Pretreatment clinical prognostic factors for brain metastases from breast cancer treated with Gamma Knife radiosurgery.

BACKGROUND: Brain metastases significantly affect morbidity and mortality rates for patients with metastatic breast cancer. Treatment for brain metastases lengthens survival, and options such as stereotactic radiosurgery (SRS) can increase survival to 12 months or longer. This study retrospectively analyzes the prognostic factors for overall survival (OS) for patients with one or multiple brain metastases from breast cancer treated with SRS. METHODS: Between December 2001 and May 2015, 111 patients with brain metastases from breast cancer were grouped by potential prognostic factors including age at diagnosis, Karnofsky Performance Status (KPS) score, number of brain metastases, and whether or not they received adjuvant treatments such as whole brain radiotherapy (WBRT) or surgical resection. Survival rates were determined for all groups, and hazard ratios were calculated using univariate and multivariate analyses to compare differences in OS. RESULTS: Median OS was 16.8 ± 4.22 months. Univariate analysis of patients with a KPS ≤60 and multivariate analysis of KPS 70-80 showed significantly shorter survival than those with KPS 90-100 (5.9 ± 1.22 months, 21.3 ± 11.69 months, and 22.00 ± 12.56 months, P = 0.024 and < 0.001). Other results such as age ≥65 years and higher number of brain metastases trended toward shorter survival but were not statistically significant. No difference in survival was found for patients who had received WBRT in addition to SRS (P = 0.779). CONCLUSION: SRS has been shown to be safe and effective in treating brain metastases from breast cancer. We found our median survival to be 16.8 ± 4.22 months, an increase from other clinical reports. In addition, 38.4% of our population was alive at 2 years and 15.6% survived 5 years. Significant prognostic factors can help inform clinical treatment decisions. This study found that KPS was a significant prognostic indicator of OS in these patients.

Retrospective Study of Metastatic Melanoma and Renal Cell Carcinoma to the Brain with Multivariate Analysis of Prognostic Pre-Treatment Clinical Factors.

Patients with brain metastasis from renal cell carcinoma (RCC) or melanoma have historically had very poor prognoses of less than one year. Stereotactic radiosurgery (SRS) can be an effective treatment for patients with these tumors. This study analyzes the effect of pretreatment prognostic factors on overall survival (OS) for RCC and melanoma patients with metastasis to the brain treated with SRS. A total of 122 patients with brain metastases from either RCC or melanoma were grouped by age at brain metastasis diagnosis, whether they received whole brain radiation therapy (WBRT) in addition to SRS, or they underwent surgical resection, Karnofsky Performance Score (KPS), number of brain metastases, and primary tumor. Median survival times for melanoma patients and RCC patients were 8.20 ± 3.06 and 12.70 ± 2.63 months, respectively. Patients with >5 metastases had a significantly shorter median survival time (6.60 ± 2.45 months) than the reference group (1 metastasis, 10.70 ± 13.40 months, p = 0.024). Patients with KPS ≤ 60 experienced significantly shorter survival than the reference group (KPS = 90-100), with median survival times of 5.80 ± 2.46 months (p < 0.001) and 45.20 ± 43.52 months, respectively. We found a median overall survival time of 12.7 and 8.2 months for RCC and melanoma, respectively. Our study determined that a higher number of brain metastases (>5) and lower KPS were statistically significant predictors of a lower OS prognosis.

Prolonged Survival following Repetitive Stereotactic Radiosurgery in a Patient with Intracranial Metastatic Renal Cell Carcinoma.

Patients with metastatic renal cell carcinoma (RCC) to the brain have a very poor prognosis of three months if left untreated. SRS is an effective treatment modality in numerous patients. This case exemplifies the utility of stereotactic radiosurgery (SRS) in prolonging survival and maintaining quality of life in a patient with RCC. This 64-year-old female patient initially presented to her primary care physician 22 months after a left nephrectomy for RCC with complaints of mild, intermittent headaches and difficulty with balance. An MRI revealed five cerebellar lesions suspicious for intracranial metastasis. The patient's first GKRS treatment targeted four lesions with 22 Gy at the 50% isodose line. She underwent a total of seven GKRS treatments over the next 60 months for recurrent metastases to the brain. 72 months and 12 months have now passed since her brain metastases were first discovered and since her last GKRS treatment, respectively, and this woman is alive with considerable quality of life and no evidence of metastatic reoccurrence. This case shows that repeated GKRS treatments, with minimal surgical intervention, can effectively treat multiple intracranial lesions in select patients, prolonging survival and avoiding iatrogenic neurocognitive decline while maintaining a high quality of life.

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.

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.

Gamma knife radiosurgery treatment for metastatic melanoma of the trigeminal nerve and brainstem: a case report and a review of the literature.

Objective and Importance. Brainstem metastases (BSMs) are uncommon but serious complications of some cancers. They cause significant neurological deficit, and options for treatment are limited. Stereotactic radiosurgery (SRS) has been shown to be a safe and effective treatment for BSMs that prolongs survival and can preserve or in some cases improve neurological function. This case illustrates the use of repeated SRS, specifically Gamma Knife radiosurgery (GKRS) for management of a unique brainstem metastasis. Clinical Presentation. This patient presented 5 years after the removal of a lentigo maligna melanoma from her left cheek with left sided facial numbness and paresthesias with no reported facial weakness. Initial MRI revealed a mass on the left trigeminal nerve that appeared to be a trigeminal schwannoma. Intervention. After only limited response to the first GKRS treatment, a biopsy of the tumor revealed it to be metastatic melanoma, not schwannoma. Over the next two years, the patient would receive 3 more GKRS treatments. These procedures were effective in controlling growth in the treated areas, and the patient has maintained a good quality of life. Conclusion. GKRS has proven in this case to be effective in limiting the growth of this metastatic melanoma without acute adverse effects.

Long-Term Survival and Improved Quality of Life following Multiple Repeat Gamma Knife Radiosurgeries for Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature.

The management of glioblastoma multiforme (GBM) is in most cases complex and must be specifically tailored to the needs of the patient with the goals of extended survival and improved quality of life. Despite advancements in therapy, treatment outcomes remain almost universally poor. Salvage treatment options for the recurrence of the disease is an area of intense study. The following case highlights the utility of Gamma Knife Radiosurgery (GKRS) as a salvage treatment. In this clinical situation, three sequential GKRS treatments led to prolonged survival (beyond four years after diagnosis) and improved quality of life in a patient who was unable to receive further chemotherapy regimens and was unwilling to undergo further aggressive resection. To date, there have been few reports of three or more sequential GKRS treatment sessions utilized as salvage therapy for recurrent GBM in patients who can no longer tolerate chemotherapy. This report provides evidence that aggressive local treatment with GKRS at the time of recurrence may be appropriate, depending on a patient's individual clinical situation, and can lead to prolonged survival and improved quality of life.

Gamma knife radiosurgery for typical trigeminal neuralgia: An institutional review of 108 patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A review of the clinical outcomes for patients diagnosed with brainstem metastasis and treated with stereotactic radiosurgery.

Only 3%-5% of all brain metastases are located in the brainstem. We present a comprehensive review of the clinical outcomes from modern studies that treated patients with brainstem metastasis using either a Gamma Knife or a linear accelerator-based stereotactic radiosurgery. The median survival time of patients was compared to better understand what clinical or treatment factors are predictive of improved survival. This information can then be utilized to optimize patient care. The data suggests that higher prescribed marginal dose and the associated greater local control of brainstem lesions are associated with longer patient survival. Further research is necessary to better describe the most effective dose for individual brainstem lesions and to tailor optimum therapy to specific patient subgroups.

Clinical outcomes of gamma knife radiosurgery in the salvage treatment of patients with recurrent high-grade glioma.

BACKGROUND: Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy. METHODS: Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed. RESULTS: After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity. CONCLUSIONS: Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating patients in specific clinical situations.

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.

Long-Term Survival of a Patient with Brainstem and Recurrent Brain Metastasis from Stage IV Nonsmall Cell Lung Cancer Treated with Multiple Gamma Knife Radiosurgeries and Craniotomies: A Case Report and Review of the Literature.

The prognosis of patients diagnosed with stage IV nonsmall cell lung cancer that have brain and brainstem metastasis is very poor, with less than a third surviving a year past their initial date of diagnosis. We present the rare case of a 57-year-old man who is a long-term survivor of brainstem and recurrent brain metastasis, after aggressive treatment. He is now five and a half years out from diagnosis and continues to live a highly functional life without evidence of disease. Four separate Gamma Knife stereotactic radiosurgeries in conjunction with two craniotomies were utilized since his initial diagnosis to treat recurrent brain metastasis while chemoradiation therapy and thoracic surgery were used to treat his primary disease in the right upper lung. In his situation, Gamma Knife radiosurgery proved to be a valuable, safe, and effective tool for the treatment of multiply recurrent brain metastases within critical normal structures.

A concise review of the efficacy of stereotactic radiosurgery in the management of melanoma and renal cell carcinoma brain metastases.

Melanoma and renal cell carcinoma have a well-documented tendency to develop metastases to the brain. Treating these lesions has traditionally been problematic, because chemotherapy has difficulty crossing the blood brain barrier and whole brain radiation therapy (WBRT) is a relatively ineffective treatment against these radioresistant tumor histologies. In recent years, stereotactic radiosurgery (SRS) has emerged as an effective and minimally-invasive treatment modality for irradiating either single or multiple intracranial structures in one clinical treatment setting. For this reason, we conducted a review of modern literature analyzing the efficacy of SRS in the management of patients with melanoma and renal cell carcinoma brain metastases. In our analysis we found SRS to be a safe, effective and attractive treatment modality for managing radioresistant brain metastases and highlighted the need for randomized trials comparing WBRT alone vs. SRS alone vs. WBRT plus SRS in treating patients with radioresistant brain metastases.

Long-term survival after gamma knife radiosurgery in a case of recurrent glioblastoma multiforme: a case report and review of the literature.

The management of recurrent glioblastoma is highly challenging, and treatment outcomes remain uniformly poor. Glioblastoma is a highly infiltrative tumor, and complete surgical resection of all microscopic extensions cannot be achieved at the time of initial diagnosis, and hence local recurrence is observed in most patients. Gamma Knife radiosurgery has been used to treat these tumor recurrences for select cases and has been successful in prolonging the median survival by 8-12 months on average for select cases. We present the unique case of a 63-year-old male with multiple sequential recurrences of glioblastoma after initial standard treatment with surgery followed by concomitant external beam radiation therapy and chemotherapy (temozolomide). The patient was followed clinically as well as with surveillance MRI scans at every 2-3-month intervals. The patient underwent Gamma Knife radiosurgery three times for 3 separate tumor recurrences, and the patient survived for seven years following the initial diagnosis with this aggressive treatment. The median survival in patients with recurrent glioblastoma is usually 8-12 months after recurrence, and this unique case illustrates that aggressive local therapy can lead to long-term survivors in select situations. We advocate that each patient treatment at the time of recurrence should be tailored to each clinical situation and desire for quality of life and improved longevity.

Effect of pretreatment clinical factors on overall survival in glioblastoma multiforme: a Surveillance Epidemiology and End Results (SEER) population analysis.

BACKGROUND: Glioblastoma Multiforme (GBM) is one of the most aggressive primary brain tumors and is associated with a dismal prognosis. The median survival after the primary diagnosis remains poor, even after multimodal treatment approaches. However, a few patients have been reported to have long term survival greater than three years. A number of studies have attempted to define factors capable of predicting long term outcomes in specific patient groups. This article reports the outcomes of a very large group of patients diagnosed with GBM, and analyzes specific prognostic factors known to influence survival in these patients. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute (NCI) to investigate various patient-related and treatment-related factors that could influence the long term survival in patients diagnosed with glioblastoma. A total of 34,664 patients aged 20 years or older with a diagnosis of GBM during the years 1973 to 2008 were studied. Overall survival outcomes were examined with Kaplan-Meier survival analysis and Cox hazard models. RESULTS: Asian/Pacific Islanders had a better survival compared to the white population (P = <0.001). Patients diagnosed with GBM during the years 2000 to 2008 had a superior survival rate when compared with earlier decades (P = <0 .001). Statistically significant improvements in overall survival were also found for patients who received surgical resections, and adjuvant radiation treatment versus no radiation (P-values <0.001). Young age was also found to be highly predictive of improved overall survival rates when separated into age groups as well as when studied as a continuous variable. CONCLUSIONS: Clinical pretreatment and treatment factors, including young age at diagnosis, Asian/Pacific Islander ethnicity, recent year of diagnosis, surgical resection and the use of adjuvant radiation therapy favorably influence survival in patients diagnosed with glioblastoma. TRIAL REGISTRATION: All data were obtained from the United States Surveillance Epidemiology and End Results (SEER) database.

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.

A Review of Novel Systemic Therapies and Brain Radiosurgery for Metastatic Melanoma.

Melanoma is a prevalent and particularly aggressive form of skin cancer. Although local disease can be treated well with excision, metastatic extracranial and intracranial disease can be very difficult to treat. Systemic therapies for melanoma have only recently led to statistically significant increases in overall survival with drugs such as Ipilimumab and Vemurafenib. Additionally, melanoma has been classically described as a relatively radio-resistant malignancy. Because of the potential radio-resistance, stereotactic radiosurgery has been widely utilized for intracranial brain metastases and clinical data has revealed excellent rates of local tumor control and tolerability with these highly focused radiation doses.

Olfactory neuroblastoma treated by endoscopic surgery followed by combined external beam radiation and gamma knife for optic nerve and chiasm sparing: a case report.

We describe the multimodality treatment regimen of a 53-year-old man diagnosed with olfactory neuroblastoma (Kadish stage C) in the right nasal cavity extending into the ethmoid sinus and across the cribriform plate. Endoscopic surgery for tumor resection was followed by a combination of external beam radiotherapy and stereotactic radiosurgery boost with concurrent chemotherapy. The novel combination of dual radiation therapies allowed for the preservation of the nearby optic structures while providing an adequate dosage to a sufficient volume of the afflicted tissue.

Feasibility of multiple repeat gamma knife radiosurgeries for trigeminal neuralgia: a case report and review of the literature.

Treatment options for trigeminal neuralgia (TN) must be customized for the individual patient, and physicians must be aware of the medical, surgical, and radiation treatment modalities to prescribe optimal treatment courses for specific patients. The following case illustrates the potential for gamma knife radiosurgery (GKRS) to be repeated multiple times for the purpose of achieving facial pain control in cases of TN that have been refractory to other medical and surgical options, as well as prior GKRS. The patient described failed to achieve pain control with initial GKRS, as well as medical and surgical treatments, but experienced significant pain relief for a period of time with a second GKRS procedure and later underwent a third procedure. Only a small subset of patients have reportedly undergone more than two GKRS for TN; thus, further research and long-term clinical followup will be valuable in determining its usefulness in specific clinical situations.

Multimodality treatment of brain metastases: an institutional survival analysis of 275 patients.

BACKGROUND: Whole brain radiation therapy (WBRT), surgical resection, stereotactic radiosurgery (SRS), and combinations of the three modalities are used in the management of patients with metastatic brain tumors. We present the previously unreported survival outcomes of 275 patients treated for newly diagnosed brain metastases at Cancer Care Northwest and Gamma Knife of Spokane between 1998 and 2008. METHODS: The effects treatment regimen, age, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS), primary tumor histology, number of brain metastases, and total volume of brain metastases have on patient overall survival were analyzed. Statistical analysis was performed using Kaplan-Meier survival curves, Andersen 95% confidence intervals, approximate confidence intervals for log hazard-ratios, and multivariate Cox proportional hazard models. RESULTS: The median clinical follow up time was 7.2 months. On multivariate analysis, survival statistically favored patients treated with SRS alone when compared to patients treated with WBRT alone (p<0.001), patients treated with resection with SRS when compared to patients treated with SRS alone (p=0.020), patients in ECOG-PS class 0 when compared to patients in ECOG-PS classes 2 (p=0.04), 3 (p<0.001), and 4 (p<0.001), patients in the non-small-cell lung cancer group when compared to patients in the combined melanoma and renal-cell carcinoma group (p<0.001), and patients with breast cancer when compared to patients with non-small-cell lung cancer (p<0.001). CONCLUSIONS: In our analysis, patients benefited from a combined modality treatment approach and physicians must consider patient age, performance status, and primary tumor histology when recommending specific treatments regimens.