文章：

BRAF、NRAS、NF1或CKIT非重叠体细胞突变对转移性黑色素瘤免疫检查点抑制剂治疗期间脑转移发生率及预后的影响

The Effect of Non-Overlapping Somatic Mutations inBRAF,NRAS,NF1, orCKITon the Incidence and Outcome of Brain Metastases during Immune Checkpoint Inhibitor Therapy of Metastatic Melanoma

原文发布日期：30 January 2024

DOI: 10.3390/cancers16030594

类型: Article

开放获取: 是

英文摘要：

Previous studies suggested that somaticBRAFandNRASmutations in metastatic melanoma increase the risk for brain metastases. The risk related to other non-overlapping “driver” mutations is unknown. We performed a retrospective evaluation of the incidence, timing, and outcome of brain metastases in a population of melanoma patients that underwent uniform next-gen sequencing. All patients were treated with initial checkpoint inhibitor therapy. Seventeen of 88 patients (20.0%) developed brain metastases. Eleven patients had brain metastases at diagnosis (12.9%). These were all patients withBRAF V600orNF1mutations. Only six patients withNRAS,NF1,KIT, orBRAFmutations (including fusions/internal rearrangements experienced delayed CNS progression following immunotherapy (7.1%)). No “quadruple negative” patient developed brain metastases. Patients with brain metastases at diagnosis had a better outcome than those with delayed intracranial progression. Current predictive markers, (LDH, tumor mutation burden, and PDL1) were poorly correlated with the development of brain metastases. Treatment with immunotherapy appears to reduce the incidence of brain metastases. Next-gen molecular sequencing of tumors in metastatic melanoma patients was useful in identifying genetic subpopulations with an increased or reduced risk of brain metastases. This may allow eventual personalization of screening strategies.

摘要翻译： 

先前的研究表明，转移性黑色素瘤中的体细胞BRAF和NRAS突变会增加脑转移的风险。与其他非重叠“驱动”突变相关的风险尚不清楚。我们对一组接受统一二代测序的黑色素瘤患者进行了回顾性评估，分析了脑转移的发生率、时间及预后。所有患者均接受了初始检查点抑制剂治疗。88例患者中有17例（20.0%）发生脑转移，其中11例在诊断时即存在脑转移（12.9%），这些患者均携带BRAF V600或NF1突变。仅有6例携带NRAS、NF1、KIT或BRAF突变（包括融合/内部重排）的患者在免疫治疗后出现延迟性中枢神经系统进展（7.1%）。未发现“四重阴性”患者发生脑转移。诊断时即存在脑转移的患者预后优于出现延迟性颅内进展的患者。现有预测标志物（LDH、肿瘤突变负荷和PDL1）与脑转移的发生相关性较弱。免疫治疗似乎降低了脑转移的发生率。对转移性黑色素瘤患者进行肿瘤二代分子测序有助于识别脑转移风险升高或降低的遗传亚群，这可能为未来个体化筛查策略的制定提供依据。

原文链接：

The Effect of Non-Overlapping Somatic Mutations inBRAF,NRAS,NF1, orCKITon the Incidence and Outcome of Brain Metastases during Immune Checkpoint Inhibitor Therapy of Metastatic Melanoma