BRAF V600 Mutation and BRAF Kinase Inhibitors in Conjunction With Stereotactic Radiosurgery for Intracranial Melanoma Metastases: A Multicenter Retrospective Study

Mastorakos, Panagiotis; Xu, Zhiyuan; Yu, James B.; Hess, Judith; Qian, Jack M.; Chatrath, Ajay; Taylor, Davis G.; Kondziolka, Douglas; Warnick, Ronald E.; Chiang, Veronica; Sheehan, Jason P.

doi:10.1093/neuros/nyy203

Cited by 32 publications

(50 citation statements)

References 57 publications

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“…Vemurafenib and dabrafenib (BRAF inhibitors) alone or dabrafenib plus trametinib have shown excellent intracranial responses (119)(120)(121)(122)(123)(124)(125). Comparative studies have suggested combination of SRS and BRAF inhibitors resulting in better outcome for BRAF-mutant melanoma patients (126)(127)(128)(129)(130). Improved local control as well as superior median survival with BRAFi with SRS particularly when used concurrently or initiated after SRS (126)(127)(128)(129)(130).…”

Section: Melanomamentioning

confidence: 99%

“…Comparative studies have suggested combination of SRS and BRAF inhibitors resulting in better outcome for BRAF-mutant melanoma patients (126)(127)(128)(129)(130). Improved local control as well as superior median survival with BRAFi with SRS particularly when used concurrently or initiated after SRS (126)(127)(128)(129)(130). Side effects remains a concern as intracranial hemorrhage and radionecrosis has been associated with the SRS in conjunction with BRAF inhibitors (126,131).…”

Section: Melanomamentioning

confidence: 99%

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Tumor Primary Site and Histology Subtypes Role in Radiotherapeutic Management of Brain Metastases

Khan

Arooj

et al. 2020

Front. Oncol.

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Randomized controlled trials have failed to report any survival advantage for WBRT combined with SRS in the management of brain metastases, despite the enhanced local and distant control in comparison to each treatment alone. Literature review have revealed important role of primary histology of the tumor when dealing with brain metastases. NSCLC responds better to combined approach even when there was only single brain metastasis present while breast cancer has registered better survival with SRS alone probably due to better response of primary tumor to advancement in surgical and chemotherapeutic agents. Furthermore, mutation status (EGFR/ALK) in lung cancer and receptor status (ER/PR/HER2) in breast cancer also exhibit diversity in their response to radiotherapy. Radioresistant tumors like renal cell carcinoma and melanoma brain metastases have achieved better results when treated with SRS alone. Secondly, single brain metastasis may benefit from local and distant brain control achieved with combined treatment. These diverse outcomes suggest a primary histology-based analysis of the radiotherapy regimens (WBRT, SRS, or their combination) would more ideally establish the role of radiotherapy in the management of brain metastases. Molecularly targeted therapeutic and immunotherapeutic agents have revealed synergism with radiation therapy particularly SRS in treating cancer patients with brain metastases. Clinical updates in this regard have also been reviewed.

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Section: Melanomamentioning

confidence: 99%

Section: Melanomamentioning

confidence: 99%

Tumor Primary Site and Histology Subtypes Role in Radiotherapeutic Management of Brain Metastases

Khan

Arooj

et al. 2020

Front. Oncol.

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“…However, whether the addition of BRAF/MEK inhibitors to SRS is synergistic and better than SRS alone has yet to be determined. Several retrospective studies have revealed conflicting outcomes regarding the synergistic efficacy of BRAF/MEK inhibitors plus SRS in the management of MBM ( 55 – 62 ). Here, we attempt to address this issue by systematically reviewing the literature and performing meta-analysis of the outcomes for a better clinical perspective.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…As compared with wild-type BRAF, BRAF mutation is an independent predictor of better prognosis in patients with melanoma brain metastases receiving SRS (11). On the other hand, the combination of SRS and immune checkpoint inhibitor (ani-PD-1 antibody or anti-CTLA-4 antibody) is also associated with reduction of distant intracranial failures compared with SRS alone or SRS with BRAF inhibitor (12).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effectiveness of Immunoradiotherapy on Brain-metastatic BRAF/MEK Inhibitor-resistant Melanoma with Balloon Cell Change

Goto¹,

Shimauchi²,

Fukuchi³

et al. 2019

Acta Derm Venerol

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Wet wrap therapy, based on skin application of a double layer of tubular bandages or gauze with a moist first inner layer and a dry second outer layer, is utilized to treat various pruritic conditions, in particular severe and refractory atopic dermatitis. This review, by literature search, evaluates current knowledge about wet wrap therapy. Wet wrap therapy superimposed topical corticosteroids appears more efficient than emollients only, at least for short-time treatments. Despite higher efficacy, there is a tendency towards more frequent infections when topical corticosteroids are covered with wet wrap bandages compared to emollients only. While temporary suppression of hypothalamic-pituitary-adrenocortical-axis was seen due to systemic bioactivity of corticosteroids, no long-term observation studies on putative adverse effects were identified. One hypothesis suggests that wet wrap therapy may trigger increased lamellar body secretion resulting in recovery of the damaged intercellular lipid laminar structure. Otherwise, little investigation on mechanisms exists.

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BRAF V600 Mutation and BRAF Kinase Inhibitors in Conjunction With Stereotactic Radiosurgery for Intracranial Melanoma Metastases: A Multicenter Retrospective Study

Cited by 32 publications

References 57 publications

Tumor Primary Site and Histology Subtypes Role in Radiotherapeutic Management of Brain Metastases

Tumor Primary Site and Histology Subtypes Role in Radiotherapeutic Management of Brain Metastases

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

Therapeutic Effectiveness of Immunoradiotherapy on Brain-metastatic BRAF/MEK Inhibitor-resistant Melanoma with Balloon Cell Change

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