癌症相关静脉血栓栓塞（VTE）是肿瘤费用、发病率和死亡率的主要来源。识别高危患者进行预防性抗凝治疗具有挑战性，并且增加了临床医生的负担。循环肿瘤 DNA (ctDNA) 测序分析（“液体活检”）已得到广泛应用，但其在 VTE 预测中的效用尚不清楚。在这里，我们分析了三个血浆测序队列：由 4,141 名非小细胞肺癌 (NSCLC) 或乳腺癌、胰腺癌和其他癌症患者组成的泛癌发现队列；由 1,426 名患有相同癌症类型的患者组成的前瞻性验证队列；以及由 463 名晚期 NSCLC 患者组成的国际普遍性队列。 ctDNA 检测与 VTE 相关，与临床和放射学特征无关。基于液体活检数据训练的机器学习模型优于之前的风险评分（发现、验证和普遍性 c 指数分别为 0.74、0.73 和 0.67，而 Khorana 评分为 0.57、0.61 和 0.54）。在现实世界数据中，如果检测到 ctDNA，抗凝与较低的 VTE 率相关（n = 2,522，调整后的风险比 (HR) = 0.50，95% 置信区间 (CI)：0.30-0.81）； ctDNA- 患者 (n = 1,619) 未从抗凝治疗中获益（调整后 HR = 0.89，95% CI：0.40-2.0）。这些结果提供了初步证据，表明除了临床参数之外，液体活检还可以改善 VTE 风险分层。需要进行介入性、随机前瞻性研究来确认液体活检在指导癌症患者抗凝治疗方面的临床效用。© 2024。作者。

Cancer-associated venous thromboembolism (VTE) is a major source of oncologic cost, morbidity and mortality. Identifying high-risk patients for prophylactic anticoagulation is challenging and adds to clinician burden. Circulating tumor DNA (ctDNA) sequencing assays ('liquid biopsies') are widely implemented, but their utility for VTE prognostication is unknown. Here we analyzed three plasma sequencing cohorts: a pan-cancer discovery cohort of 4,141 patients with non-small cell lung cancer (NSCLC) or breast, pancreatic and other cancers; a prospective validation cohort consisting of 1,426 patients with the same cancer types; and an international generalizability cohort of 463 patients with advanced NSCLC. ctDNA detection was associated with VTE independent of clinical and radiographic features. A machine learning model trained on liquid biopsy data outperformed previous risk scores (discovery, validation and generalizability c-indices 0.74, 0.73 and 0.67, respectively, versus 0.57, 0.61 and 0.54 for the Khorana score). In real-world data, anticoagulation was associated with lower VTE rates if ctDNA was detected (n = 2,522, adjusted hazard ratio (HR) = 0.50, 95% confidence interval (CI): 0.30-0.81); ctDNA- patients (n = 1,619) did not benefit from anticoagulation (adjusted HR = 0.89, 95% CI: 0.40-2.0). These results provide preliminary evidence that liquid biopsies may improve VTE risk stratification in addition to clinical parameters. Interventional, randomized prospective studies are needed to confirm the clinical utility of liquid biopsies for guiding anticoagulation in patients with cancer.© 2024. The Author(s).