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 <0.00001), from the time of brain metastasis diagnosis (BM survival: HR 0.65 [0.54, 0.78], p < 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.

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.

scholarly journals CMET-32. THE EFFECT OF IMMUNOTHERAPY TREATMENT ON LOCAL CONTROL FOR MELANOMA BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi45-vi46 ◽  
Author(s):  
Luke Pearson ◽  
Steven Nguyen ◽  
Andrew Keller ◽  
Sean All ◽  
Hanisha Patel ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Melanoma Brain Metastases

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.

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