scholarly journals The effect of targeted agents on outcomes in patients with brain metastases from renal cell carcinoma treated with Gamma Knife surgery

2012 ◽  
Vol 116 (5) ◽  
pp. 978-983 ◽  
Author(s):  
D. Clay Cochran ◽  
Michael D. Chan ◽  
Mebea Aklilu ◽  
James F. Lovato ◽  
Natalie K. Alphonse ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Gamma Knife ◽  
Local Control ◽  
Renal Cell ◽  
Local Failure ◽  
Targeted Agents ◽  
Distant Failure

Object Gamma Knife surgery (GKS) has been reported as an effective modality for treating brain metastases from renal cell carcinoma (RCC). The authors aimed to determine if targeted agents such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and bevacizumab affect the patterns of failure of RCC after GKS. Methods Between 1999 and 2010, 61 patients with brain metastases from RCC were treated with GKS. A median dose of 20 Gy (range 13–24 Gy) was prescribed to the margin of each metastasis. Kaplan-Meier analysis was used to determine local control, distant failure, and overall survival rates. Cox proportional hazard regression was performed to determine the association between disease-related factors and survival. Results Overall survival at 1, 2, and 3 years was 38%, 17%, and 9%, respectively. Freedom from local failure at 1, 2, and 3 years was 74%, 61%, and 40%, respectively. The distant failure rate at 1, 2, and 3 years was 51%, 79%, and 89%, respectively. Twenty-seven percent of patients died of neurological disease. The median survival for patients receiving targeted agents (n = 24) was 16.6 months compared with 7.2 months (n = 37) for those not receiving targeted therapy (p = 0.04). Freedom from local failure at 1 year was 93% versus 60% for patients receiving and those not receiving targeted agents, respectively (p = 0.01). Multivariate analysis showed that the use of targeted agents (hazard ratio 3.02, p = 0.003) was the only factor that predicted for improved survival. Two patients experienced post-GKS hemorrhage within the treated volume. Conclusions Targeted agents appear to improve local control and overall survival in patients treated with GKS for metastastic RCC.

scholarly journals Stereotactic radiosurgery for intraventricular brain metastases

2014 ◽  
Vol 121 (Suppl_2) ◽  
pp. 26-34 ◽  
Author(s):  
Benjamin Farnia ◽  
K. Ranh Voong ◽  
Paul D. Brown ◽  
Pamela K. Allen ◽  
Nandita Guha-Thakurta ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Free Survival ◽  
Distant Failure

ObjectThe authors' institution previously reported a 69% rate of crude local control for surgical management of lateral ventricle metastases at the University of Texas MD Anderson Cancer Center. For comparison, the authors here report their institutional experience with use of stereotactic radiosurgery (SRS) to treat intraventricular metastases.MethodsTo identify patients with intraventricular metastases for this retrospective review, the authors queried an institutional SRS database containing the medical records of 1962 patients with 5800 brain metastases who consecutively underwent SRS from June 2009 through October 2013. End points assessed were local control (crude and locoregional), distant failure–free survival, progression-free survival, and overall survival.ResultsOf the 1962 records examined, those for 25 (1.3%) patients with 30 (0.52%) intraventricular metastases were identified. Median patient age at SRS was 55.8 years. The most common primary malignancy was renal cell carcinoma (n = 13), followed by melanoma (n = 7) and breast adenocarcinoma (n = 5). Median tumor volume was 0.75 cm3 (range 0.01–5.6 cm3). Most lesions were located in the lateral ventricles (n = 25, 83.3%) and were treated to a median dose of 20 Gy (range 14–20 Gy). A total of 12 (48%) patients received whole-brain radiation therapy, most (n = 10) before SRS. With a median follow-up of 11.4 months (range 1.6–39.2 months), the rate of crude local control was 93.3%, and the rates of 6-month and 1-year actuarial locoregional control were 85.2% and 56.2%, respectively. The median overall survival time after SRS was 11.6 months (range 1.3–38.9 months), and the 6-month and 1-year actuarial rates were 87.1% and 46.7%, respectively. Disease dissemination developed in 7 (28%) patients as a second intraventricular metastatic lesion (n = 3, 12%), leptomeningeal disease (n = 3, 12%), or both (n = 1, 4%). Radiographic changes developed in 5 (20%) patients and included necrosis (n = 2, 8%) and hemorrhage (n = 3, 12%). A primary diagnosis of renal cell carcinoma was associated with an improved rate of distant failure–free survival (p = 0.05) and progression-free survival (p = 0.08).ConclusionsSRS provides excellent local control for intraventricular metastases, with acceptable treatment-related toxicity, thereby supporting nonsurgical treatment for these lesions. The propensity for intraventricular dissemination among intraventricular metastases seems to be histologically dependent.

Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma

2008 ◽  
Vol 109 (Supplement) ◽  
pp. 122-128 ◽  
Author(s):  
John W. Powell ◽  
Chung T. Chung ◽  
Hemangini R. Shah ◽  
Gregory W. Canute ◽  
Charles J. Hodge ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Gamma Knife ◽  
Treatment Option ◽  
Renal Cell ◽  
Gamma Knife Surgery ◽  
Tumor Control ◽  
Local Progression

Object The purpose of this study was to examine the results of using Gamma Knife surgery (GKS) for brain metastases from classically radioresistant malignancies. Methods The authors retrospectively reviewed the records of 76 patients with melanoma (50 patients), renal cell carcinoma (RCC; 23 patients), or sarcoma (3 patients) who underwent GKS between August 1998 and July 2007. Overall patient survival, intracranial progression, and local progression of individual lesions were analyzed. Results The median age of the patients was 57 years (range 18–85 years) and median Karnofsky Performance Scale (KPS) score was 80 (range 20–100). Sixty-two patients (81.6%) had uncontrolled extracranial disease. A total of 303 intracranial lesions (average 3.97 per patient, range 1–27 lesions) were treated using GKS. More than 3 lesions were treated in 30 patients (39.5%). Median GKS tumor margin dose was 18 Gy (range 8–30 Gy). Thirty-seven patients (48.7%) underwent whole brain radiation therapy. The actuarial 12-month rate for freedom from local progression for individual lesions was 77.7% and was significantly higher for RCC compared with melanoma (93.6 vs 63.0%; p = 0.001). The percentage of coverage of the prescribed dose to target volume was the only treatment–related variable associated with local control: 12-month actuarial rate of freedom from local progression was 71.4% for lesions receiving ≥ 90% coverage versus 0.0% for lesions receiving < 90% (p = 0.00048). Median overall survival was 5.1 months after GKS and 8.4 months after the discovery of brain metastases. Univariate analysis revealed that KPS score (p = 0.000004), recursive partitioning analysis class (p = 0.00043), and single metastases (p = 0.028), but not more than 3 metastases, to be prognostic factors of overall survival. The KPS score remained significant after multivariate analysis. Overall survival for patients with a KPS score ≥ 70 was 7.1 months compared with 1.3 months for a KPS score ≤ 60 (p = 0.013). Conclusions Gamma Knife surgery is an effective treatment option for patients with radioresistant brain metastases. In this setting, KPS score appeared to be a more important factor in predicting survival than having > 3 metastases. Higher rates of local tumor control were achieved for RCC in comparison with melanoma, and this may have an effect on survival in some patients. Although outcomes generally remained poor in this study population, these results suggest that GKS can be considered as a treatment option for many patients with radioresistant brain metastases, even if these patients have multiple lesions.

Stereotactic Radiosurgery for Patients with “Radioresistant” Brain Metastases

Neurosurgery ◽  
2002 ◽  
Vol 51 (3) ◽  
pp. 656-667 ◽  
Author(s):  
Paul D. Brown ◽  
Cerise A. Brown ◽  
Bruce E. Pollock ◽  
Deborah A. Gorman ◽  
Robert L. Foote
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Stereotactic Radiosurgery ◽  
Median Survival ◽  
Local Control ◽  
Renal Cell ◽  
Class I

Abstract OBJECTIVE Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be “radioresistant” on the basis of histological examination. METHODS We reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases. RESULTS The median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P &lt; 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027). CONCLUSION Well-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.

Gamma knife radiosurgery for renal cell carcinoma brain metastases

2002 ◽  
Vol 97 ◽  
pp. 489-493 ◽  
Author(s):  
Laura Hernandez ◽  
Lucia Zamorano ◽  
Andrew Sloan ◽  
James Fontanesi ◽  
Simon Lo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Gamma Knife ◽  
Median Survival ◽  
Renal Cell ◽  
Univariate Analysis ◽  
Gamma Knife Radiosurgery ◽  
Content Type ◽  
Fine Print

Object. The purpose of this study was to clarify the effectiveness of gamma knife radiosurgery (GKS) in achieving a partial or complete remission of so-called radioresistant metastases from renal cell carcinoma (RCC) and to propose guidelines for optimal treatment Methods. During a 5-year period, 29 patients (19 male and 10 female) with 92 brain metastases from RCC underwent GKS. The median tumor volume was 4.7 cm3 (range 0.5–14.5 cm3). Fourteen patients (48%) also underwent whole-brain radiotherapy (WBRT) before GKS, and two patients (6.8%) after GKS. The mean GKS dose delivered to the 50% isodose at the tumor margin was 16.8 Gy (range 13–30 Gy). All cases were categorized according to the Recursive Partitioning Analysis (RPA) classification for brain metastases. Univariate analysis was performed to determine significant prognostic factors and survival. The overall median survival was 7 months after GKS treatment. Age, sex, Karnofsky Performance Scale score, and controlled primary disease were not predictors of survival. Combined WBRT/GKS resulted in median survival of 18, 8.5, and 5.3 months for RPA Classes I, II, and III, respectively, compared with the median survival 7.1, 4.2, and 2.3 months for patients treated with WBRT alone. Conclusions. These results suggest that WBRT combined with GKS may improve survival in patients with brain metastases from RCC. Furthermore, this improvement in survival was seen in all RPA classes.

CYBERKNIFE FOR BRAIN METASTASES OF MALIGNANT MELANOMA AND RENAL CELL CARCINOMA

Neurosurgery ◽  
2009 ◽  
Vol 64 (suppl_2) ◽  
pp. A26-A32 ◽  
Author(s):  
Wendy Hara ◽  
Phuoc Tran ◽  
Gordon Li ◽  
Zheng Su ◽  
Putipun Puataweepong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Malignant Melanoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Local Control ◽  
Renal Cell ◽  
Systemic Disease ◽  
Karnofsky Performance Scale ◽  
Actuarial Survival ◽  
The Mean

Abstract OBJECTIVE To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with brain metastases of malignant melanoma and renal cell carcinoma. METHODS We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between March 1999 and December 2005. Sixty-two patients with 145 brain metastases of renal cell carcinoma or melanoma were identified. RESULTS The median follow-up period was 10.5 months. Forty-four patients had malignant melanoma, and 18 patients had renal cell carcinoma. The median age was 57 years, and patients were classified as recursive partitioning analysis Class 1 (6 patients), 2 (52 patients) or 3 (4 patients). Thirty-three patients had been treated systemically with either chemotherapy or immunotherapy, and 33 patients were taking corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL (range, 0.02–35.7 mL), and the mean prescribed dose was 20 Gy (range, 14–24 Gy). The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12 months was 57 and 37%, respectively. On multivariate analysis, Karnofsky Performance Scale score (P &lt; 0.01) and previous immunotherapy/clinical trial (P = 0.01) significantly affected overall survival. One-year intracranial progression-free survival was 38%, and local control was 87%. Intracranial control was impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P = 0.01), and control of the primary at the time of SRS (P = 0.02). Surgical resection had no effect on intracranial or local control. Radiographic evidence of radiation necrosis developed in 4 patients (6%). CONCLUSION CyberKnife radiosurgery provided excellent local control with acceptable toxicity in patients with melanoma or renal cell brain metastases. Initial SRS alone appeared to be a reasonable option, as survival was dictated by systemic disease.

Repeated gamma knife surgery for multiple brain metastases from renal cell carcinoma

2002 ◽  
Vol 97 (4) ◽  
pp. 785-793 ◽  
Author(s):  
Berndt Wowra ◽  
Michael Siebels ◽  
Alexander Muacevic ◽  
Friedrich Wilhelm Kreth ◽  
Andreas Mack ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Gamma Knife ◽  
Renal Cell ◽  
Radiation Toxicity ◽  
Content Type ◽  
Multiple Brain Metastases ◽  
Fine Print

Object. The aim of this study was to evaluate the therapeutic profile of repeated gamma knife surgery (GKS) for renal cell carcinoma that has metastasized to the brain on multiple occasions. Methods. Data from this study were culled from a single institution and cover a 6-year period of outpatient radiosurgery. A standard protocol for indication, dose planning, and follow up was established. In cases of distant or local recurrences, radiosurgery was undertaken repeatedly (up to six times in one individual). Seventy-five patients harboring 350 cerebral metastases were treated. Relief from pretreatment neurological symptoms occurred in 72% of patients within a few days or a few weeks after the procedure. The actuarial local tumor control rate after the initial GKS was 95%. In patients free from relapse of intracranial metastases after repeated radiosurgery, long-term survival was 91% after 4 years; median survival was 11.1 ± 3.2 months after radiosurgery and 4.5 ± 1.1 years after diagnosis of the primary kidney cancer. Survival following radiosurgery was independent of patient age and sex, side of the renal cell carcinoma, pretreatment of the cerebrum by using radiotherapy or surgery, number of brain metastases and their synchronization with the primary renal cell carcinoma, and the frequency of radiosurgical procedures. In contrast, survival was dependent on the patient's clinical performance score and the extracranial tumor status. Tumor bleeding was observed in seven patients (9%) and late radiation toxicity (LRT) in 15 patients (20%). Treatment-related morbidity was moderate and mostly transient. Late radiation toxicity was encountered predominantly in long-term survivors. Conclusions. Outpatient repeated radiosurgery is an effective and only minimally invasive treatment for multiple brain metastases from renal cell cancer and is recommended as being the method of choice to control intracranial disease, especially in selected patients with limited extracranial disease. Physicians dealing with such patients should be aware of the characteristic aspects of LRT.

scholarly journals Survival Benefit With Resection of Brain Metastases From Renal Cell Carcinoma in the Setting of Molecular Targeted Therapy and Immune Therapy

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Mark A Damante ◽  
Kristin Huntoon ◽  
Thomas Olencki ◽  
Bradley Elder
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Survival Benefit ◽  
Treatment Modalities ◽  
Targeted Agents ◽  
Systemic Treatments ◽  
Molecular Targeted Agents

Abstract INTRODUCTION Patient survival with renal cell carcinoma (RCC) has improved with the use of molecular targeted agents and immunotherapy. Given the potential activity of these agents in treating brain metastases (BM), the role of aggressive local management with surgery and/or radiation may diminish. This study evaluated the benefit of aggressive local therapy of RCC BM in the setting of molecular targeted agents and/or immunotherapy. METHODS A retrospective single-center review between 2011 and 2018 identified 1659 patients treated for RCC. The study group included patients that developed BM and received molecular targeted agents and/or immunotherapy during the course of their disease. Data analyzed included demographic information, systemic treatments, and local BM treatment modalities. Kaplan-Meier curves and log-rank values were used to assess progression free survival (PFS) and overall survival (OS) following RCC and BM diagnosis. RESULTS Of 1659 patients, 108 (6.5%) were diagnosed with BM during their clinical course. Mean OS from diagnosis of RCC for these 108 patients was 44.5 ± 40.1 mo, with 1-, 3-, and 5-yr survival of 76.9%, 43.3%, and 38.1%. All patients were treated with molecular targeted agents and/or immunotherapy. OS was analyzed based on three treatment groups: systemic therapy only (26.1 ± 31.2, n = 21), systemic and radiotherapy (41.4 ± 34.9, n = 54), and systemic and radiotherapy plus BM resection (61.4 ± 46.9, n = 33). Survival benefit was seen with surgery compared to systemic therapy alone (P = .002) and the systemic and radiotherapy cohort (P = .038). PFS did not differ significantly between cohorts. Variables such as pre-treatment performance status (ECOG P = .085; KPS P = .231), number of BM (median 2, P = .685) and status of systemic disease at the time of BM diagnosis did not differ significantly. CONCLUSION In the setting of molecular targeted agents and immunotherapy, BM resection maximizes OS in surgical candidates. Prospective clinical trials are needed to elucidate activity of newer molecular targeted agents and immunotherapy in RCC BM treatment.

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