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Abstract：
Thromboembolic events (TE) are a common complication in patients with metastatic renal cell carcinoma (mRCC) and are associated with poorer clinical outcomes. However, the incidence of TE and clinical and genomic characteristics of patients with mRCC who develop this complication are poorly understood. Herein, we describe the incidence and clinical features of patients with mRCC with or without TE at our institution, and examine their association with the underlying genomic and transcriptomic characteristics of the tumor. This retrospective study included all consecutive cases of mRCC seen at our institution. A CLIA-certified lab performed tumor genomics and transcriptomics. Patients were classified based on the presence of a TE within the first year of diagnosis. Three hundred and seventy patients with mRCC were included in the study. TE was seen in 11% (42) of the patients. Patients with favorable International mRCC Database Consortium (IMDC) risk were less likely to develop a TE. In contrast, patients receiving combination treatment with a tyrosine kinase inhibitor (TKI) and an immune checkpoint inhibitor were more likely to develop a TE. No difference in overall survival among patients with or without TE was observed (52 vs. 55 months; HR 0.85, 95% CI 0.5574-1.293, p = 0.24). The most upregulated pathways in mRCC with TEs versus those without were the xenobiotic metabolism and mTORC1 signaling pathways. Our findings suggest potential biomarkers that, after external validation, could be used to better select patients who would benefit from prophylactic anticoagulation.
摘要：
血栓栓塞事件（TE）是转移性肾细胞癌（mRCC）患者的常见并发症，并与较差的临床预后相关。然而,TE的发生率以及发生这种并发症的mRCC患者的临床和基因组特征知之甚少.在这里，我们描述了在我们机构有或没有TE的mRCC患者的发病率和临床特征，并检查它们与肿瘤的潜在基因组和转录组特征的关联。这项回顾性研究包括在我们机构看到的所有连续mRCC病例。CLIA认证的实验室进行了肿瘤基因组学和转录组学。根据诊断第一年内TE的存在对患者进行分类。该研究包括三百七十例mRCC患者。在11％（42）的患者中看到TE。具有良好的国际mRCC数据库联盟（IMDC）风险的患者不太可能发生TE。相比之下,接受酪氨酸激酶抑制剂(TKI)和免疫检查点抑制剂联合治疗的患者更有可能发生TE.在有或没有TE的患者中，总生存率没有差异（52vs.55个月；HR0.85，95%CI0.5574-1.293，p=0.24）。在有TE的mRCC中，与没有TE的mRCC中最上调的途径是异种生物代谢和mTORC1信号通路。我们的研究结果表明，潜在的生物标志物，在外部验证之后,可用于更好地选择将受益于预防性抗凝的患者。
