scholarly journals P.109 Increased survival when combining BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases

2016 ◽  
Vol 43 (S2) ◽  
pp. S45-S46
Author(s):  
A Wolf ◽  
A Pavlick ◽  
M Wilson ◽  
J Silverman ◽  
D Kondziolka
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Systemic Disease ◽  
Braf Inhibitor ◽  
Braf Inhibitors ◽  
Actuarial Survival ◽  
Early Management ◽  
Melanoma Brain Metastases ◽  
The Impact

Background: The purpose of the study was to evaluate the impact of BRAF inhibitors on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases. Methods: We prospectively collected treatment outcomes for 80 patients with melanoma brain metastases who underwent SRS. Thirty-five patients harbored the BRAF mutation (BRAF-M) and 45 patients did not (BRAF-WT). Results: The median overall survival from first SRS procedure was 11.2 months if treated with a BRAF inhibitor and 4.5 months for BRAF-WT. Actuarial survival rates for BRAF-M patients on an inhibitor were 54% and 41% at 6 and 12 months after radiosurgery, in contrast to 28% and 19% for BRAF-WT. Overall survival was extended for patients on a BRAF inhibitor if initiated at or after the first SRS. The local control rate did not differ based on BRAF status and was over 90%. Patients with higher KPS, fewer treated metastases, controlled systemic disease, RPA class 1 and BRAF-M patients had extended overall survival. Conclusions: Patients with BRAF-M treated with both SRS and BRAF inhibitors, at or after SRS, have increased overall survival. As patients live longer due to more effective systemic and local therapies, close surveillance and early management of intracranial disease with SRS will become increasingly important.

Impact on overall survival of the combination of BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases

2016 ◽  
Vol 127 (3) ◽  
pp. 607-615 ◽  
Author(s):  
Amparo Wolf ◽  
Sayyad Zia ◽  
Rashika Verma ◽  
Anna Pavlick ◽  
Melissa Wilson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Braf Inhibitors ◽  
Melanoma Brain Metastases

scholarly journals Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

2015 ◽  
Vol 123 (2) ◽  
pp. 395-401 ◽  
Author(s):  
David Ly ◽  
Hilary P. Bagshaw ◽  
Christopher J. Anker ◽  
Jonathan D. Tward ◽  
Kenneth F. Grossmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Braf Inhibitor ◽  
Local Control Rate ◽  
Inhibitor Therapy ◽  
Braf Inhibitors ◽  
Whole Brain Radiation

OBJECT BRAF inhibitors improve progression-free and overall survival in patients with metastatic melanoma. Brain metastases are common, and stereotactic radiosurgery (SRS) has been used, resulting in excellent local control. Because BRAF inhibitors are associated with intracranial responses, the authors hypothesized that BRAF inhibitors would improve local control in patients with melanoma who are receiving SRS for brain metastases. METHODS The authors retrospectively identified patients with metastatic melanoma who had been tested for BRAF mutation and treated with SRS for brain metastases. Patients with previous resection, multiple brain metastases, or multiple courses of SRS were eligible. SRS was delivered in a single fraction to a median dose of 2000 cGy. Patients with a BRAF mutation were treated with a BRAF inhibitor on the basis of physician preference. RESULTS The authors identified 52 patients who were treated in 82 treatment sessions for 185 brain metastases and 13 tumor beds. At a median follow-up of 10.5 months, the 1-year local control rate was 69.2%. At 1 year, the local control rate for brain metastases in patients with BRAF mutation with BRAF treatment was 85.0%, and the local control rate for brain metastases in those without BRAF treatment was 51.5% (p = 0.0077). The rates of distant brain failure, freedom from whole-brain radiation, and overall survival were not different on the basis of BRAF mutation status or inhibitor therapy. The number of new intratumoral hemorrhages after SRS was increased significantly in patients with BRAF treatment. CONCLUSIONS Treatment with BRAF inhibitors was associated with improved local control after SRS in patients with melanoma and brain metastases. An increased number of intratumoral hemorrhages was associated with BRAF inhibitor therapy.

Early imaging radioresponsiveness of melanoma brain metastases as a predictor of patient prognosis

2018 ◽  
Vol 129 (2) ◽  
pp. 354-365 ◽  
Author(s):  
Irina Zubatkina ◽  
Pavel Ivanov
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Brain Metastases ◽  
Retrospective Analysis ◽  
Systemic Disease ◽  
Rapid Response ◽  
Slow Response ◽  
Melanoma Brain Metastases ◽  
Radiological Response ◽  
Patient Prognosis

OBJECTIVEThe aim of this study was to analyze the early radiological response of melanoma brain metastases to single high-dose irradiation and to reveal possible correlations between tumor radioresponsiveness and patient clinical outcomes.METHODSThe authors performed a retrospective analysis of the medical data for all patients with melanoma brain metastases who had undergone Gamma Knife radiosurgery (GKRS) and follow-up MRI examinations with standard protocols at regular 2- to 3-month intervals. Volumetric measurements of the metastases on pretreatment and initial posttreatment images were performed to assess the rate of early radiological response. Patients were divided into 2 groups according to the rate of response, and overall survival, local control, and the appearance of new metastases in the brain were compared in these groups using the long-rank test. Univariate and multivariate analyses were performed to identify predictors of clinical outcomes.RESULTSAfter retrospective analysis of 298 melanoma brain metastases in 78 patients, the authors determined that early radiological responses of these metastases to GKRS differ considerably and can be divided into 2 distinct groups. One group of tumors underwent rapid shrinkage after radiosurgery, whereas the other showed minor fluctuations in size (rapid- and slow-response groups, respectively). Median survival for patients with a slow response was 15.2 months compared with 6.3 months for those with a rapid response (p < 0.0001). In the multivariate analysis, improved overall survival was associated with a slow response to radiosurgery (p < 0.0001), stable systemic disease (p = 0.001), and a higher Karnofsky Performance Scale score (p = 0.001). Stratification by Recursive Partitioning Analysis, score index for radiosurgery, and diagnosis-specific Graded Prognostic Assessment classes further confirmed the difference in overall survival for patients with a slow versus rapid radiation response. Local recurrence was observed in 11% of patients with a rapid response and in 6% of patients with a slow response, at a median of more than 8 months after radiosurgery. New brain metastases were diagnosed in 67% of patients with a slow response at a median of 8.6 months after radiosurgery and in 82% of patients with a rapid response at a considerably earlier median time of 2.7 months. In the multivariate analysis, a longer time to the development of new brain metastases was associated with a slow response (p = 0.012), stable systemic disease (p = 0.034), and a single brain metastasis (p = 0.030).CONCLUSIONSMelanoma brain metastases show different early radioresponsiveness to radiosurgery. Rapid shrinkage of brain metastases is associated with poor patient prognosis, which may indicate more aggressive biological behavior of this tumor phenotype.

scholarly journals 12. OUTCOMES AFTER SURGICAL RESECTION OF MELANOMA BRAIN METASTASES IN THE AGE OF CHECKPOINT INHIBITOR TREATMENT

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii1-ii2
Author(s):  
Ramin Morshed ◽  
Jason Chung ◽  
Vivek Sudhakar ◽  
Daniel Cummins ◽  
Jacob Young ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Surgical Resection ◽  
Cox Regression ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Systemic Disease ◽  
Melanoma Brain Metastases ◽  
The Impact ◽  
First Time ◽  
Inhibitor Treatment

Abstract BACKGROUND Metastasis of melanoma to the brain is associated with poor outcomes. Recent trials demonstrate improved survival after treatment with immune checkpoint inhibitors. OBJECTIVE To examine the impact that checkpoint inhibitor treatment has on overall survival (OS) and central nervous system (CNS) progression in a cohort of patients undergoing surgical resection of melanoma brain metastases. METHODS This retrospective, single-center study included patients undergoing first-time surgical resection of melanoma brain metastases. A multivariate Cox proportional model was used to estimate the association of patient and treatment factors with OS and CNS progression. RESULTS 85 patients underwent first-time resection of 97 melanoma brain metastases with a median follow-up of 9.5 months. Checkpoint inhibitors (Pembrolizumab, Ipilimumab, and/or Nivolumab) were used in 55.1% of cases (19 pre-op; 47 post-op; median 9 cycles). Patients treated with checkpoint inhibitors had similar peri-op systemic disease status and KPS but had been treated with more systemic agents and had more instances of CNS progression prior to surgery. Median OS and time to CNS progression for the cohort were 1 year and 237 days, respectively. In a multivariate Cox regression model, age (HR 1.03 by decade; p=0.02), treatment with a checkpoint inhibitor (HR 0.27; p&lt;0.0001), prior radiotherapy (HR 2.44; p=0.007), and number of brain metastases at the time of surgery (HR 1.05 per metastasis; p=0.04) were significant predictors of OS. Checkpoint inhibitor treatment was associated with longer OS from surgery (median 3 vs 0.5 yrs, log-rank p=0.004). However, patients who underwent craniotomy after prior checkpoint inhibitor treatment had poor OS (median 0.56 yrs). Prior radiotherapy was also associated with poor OS (median 0.53 yrs). CONCLUSIONS While checkpoint inhibitor treatment was associated with improved survival in this surgical cohort of melanoma brain metastases, patients who require surgical resection after checkpoint inhibitor treatment or radiotherapy are poor surgical candidates.

scholarly journals Efficacy of BRAF Inhibitors in Combination With Stereotactic Radiosurgery for the Treatment of Melanoma Brain Metastases: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Muhammad Khan ◽  
Tao Zheng ◽  
Zhihong Zhao ◽  
Sumbal Arooj ◽  
Guixiang Liao
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Intracranial Hemorrhage ◽  
Local Control ◽  
Meta Analysis ◽  
Local Treatment ◽  
Dual Therapy ◽  
Braf Inhibitors ◽  
Melanoma Brain Metastases

BackgroundBRAF inhibitors have improved the outcome for patients with BRAF mutant metastatic melanoma and have shown intracranial responses in melanoma brain metastases. Stereotactic radiosurgery (SRS) is being used as a local treatment for melanoma brain metastasis (MBM) with better local control and survival. We searched for studies comparing the combination of two treatments with SRS alone to detect any clinical evidence of synergism.Materials and MethodsPubMed, EMBASE, Medline, and Cochrane library were searched until May 2020 for studies with desired comparative outcomes. Outcomes of interest that were obtained for meta-analysis included survival as the primary, and local control as the secondary outcome.ResultsA total of eight studies involving 976 patients with MBM were selected. Survival was significantly improved for patients receiving BRAF inhibitor plus SRS in comparison to SRS alone as assessed from the time of SRS induction (SRS survival: hazard ratio [HR] 0.67 [0.58–0.79], p &lt;0.00001), from the time of brain metastasis diagnosis (BM survival: HR 0.65 [0.54, 0.78], p &lt; 0.00001), or from the time of primary diagnosis (PD survival: HR 0.74 [0.57–0.95], p = 0.02). Dual therapy was also associated with improved local control, indicating an additive effect of the two treatments (HR 0.53 [0.31–0.93], p=0.03). Intracranial hemorrhage was higher in patients receiving BRAF inhibitors plus SRS than in those receiving SRS alone (OR, 3.16 [1.43–6.96], p = 0.004).ConclusionsBRAF inhibitors in conjunction with SRS as local treatment appear to be efficacious. Local brain control and survival improved in patients with MBM receiving dual therapy. Safety assessment would need to be elucidated further as the incidence of intracranial hemorrhage was increased.

Survival patterns following brain metastases for patients with melanoma in the targeted therapy era.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9064-9064
Author(s):  
Daniel A. Wattson ◽  
Helen Alice Shih ◽  
Andrzej Niemierko ◽  
Ryan M. Merritt ◽  
Donald P. Lawrence ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Braf Inhibitors ◽  
Actuarial Survival ◽  
Intracranial Disease ◽  
Prospective Trials ◽  
Survival Patterns ◽  
The Impact ◽  
Braf Mutant

9064 Background: Survival from metastatic melanoma (MM) has been significantly prolonged with the introduction of molecularly targeted therapy, including BRAF inhibitors (BRAFi) for patients (pts) with the V600E mutation. Here, we present the first data describing patterns of survival after diagnosis of brain metastases (BM) in a large cohort of these pts with long follow-up. Methods: A retrospective review of 191 MM pts accrued on multiple prospective trials between 2008–2012 was conducted. These trials assessed novel immunologic and targeted therapies in pts with both BRAF mutant (n=70) and wild type/unknown (n=121) tumors. We evaluated pt characteristics and the impact of systemic and BM-directed treatments. Results: Of 98 pts who developed BM, median follow-up after first BM was 7.7 months (15.5 months for the 25 living pts), and 33 were treated with BRAFi. Median duration of BRAFi use was 5.9 months (range 0.7–27.1), which preceded BM in 30%, was concurrent with first BM in 18%, and followed first BM in 52%. Ipilimumab or anti–PD-1/PD-L1 immunotherapy was given to 58% of pts who received a BRAFi and 95% of those who did not. Limited intracranial disease on initial BM presentation (defined as ≤3 lesions) occurred in 70% of BRAFi-treated pts and 74% of non-BRAFi pts, and 70% of BRAFi pts received at least one focal BM treatment (stereotactic radiosurgery or resection) compared to 75% of non-BRAFi pts. As shown in the Table, actuarial survival after BM diagnosis was prolonged among pts treated with a BRAFi. This is due primarily to the nearly 2-year median survival of pts for whom a BRAFi was initiated after BM were diagnosed. Conclusions: Survival for pts with BM from BRAF mutant MM can significantly exceed the often anticipated 4–6 months, particularly if a BRAFi is initiated after BM arise. This supports BRAFi activity in intracranial disease, and helps to inform trials currently under way testing BRAFi use among MM pts with previously diagnosed BM. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document