Khan Muhammad, Zheng Tao, Zhao Zhihong, Arooj Sumbal, Liao Guixiang
Department of Oncology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
Department of Oncology, First affiliated Hospital of Anhui Medical University, Hefei, China.
Front Oncol. 2021 Feb 22;10:586029. doi: 10.3389/fonc.2020.586029. eCollection 2020.
BRAF 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.
PubMed, 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.
A 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).
BRAF 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.
BRAF抑制剂改善了BRAF突变转移性黑色素瘤患者的预后，并在黑色素瘤脑转移中显示出颅内反应。立体定向放射外科（SRS）正被用作黑色素瘤脑转移（MBM）的局部治疗方法，具有更好的局部控制率和生存率。我们检索了比较两种治疗方法联合使用与单独使用SRS的研究，以发现协同作用的任何临床证据。
检索PubMed、EMBASE、Medline和Cochrane图书馆，直至2020年5月，查找具有所需比较结果的研究。用于荟萃分析的感兴趣的结果包括生存作为主要结果，局部控制作为次要结果。
共选择了八项涉及976例MBM患者的研究。从SRS诱导时评估，接受BRAF抑制剂加SRS的患者生存率比单独接受SRS的患者显著提高（SRS生存：风险比[HR]0.67[0.58 - 0.79]，p < 0.00001）；从脑转移诊断时评估（BM生存：HR 0.65[0.54, 0.78]，p < 0.00001）；或从初次诊断时评估（PD生存：HR 0.74[0.57 - 0.95]，p = 0.02）。联合治疗也与局部控制改善相关，表明两种治疗具有相加作用（HR 0.53[0.31 - 0.93]，p = 0.03）。接受BRAF抑制剂加SRS的患者颅内出血高于单独接受SRS的患者（比值比，3.16[1.43 - 6.96]，p = 0.004）。
BRAF抑制剂与SRS联合作为局部治疗似乎是有效的。接受联合治疗的MBM患者局部脑控制和生存率得到改善。由于颅内出血发生率增加，需要进一步阐明安全性评估。
