我们报告了一种个性化的肿瘤信息技术，名为“基于患者特异性变异的疾病预后和潜在治疗标记追踪技术”（PROPHET），利用50个患者特异性变异的深度测序，检测分子残余病（MRD），检测限度为0.004%。PROPHET与最先进的固定面板检测方法同时应用于181名初期非小细胞肺癌患者的760份血浆样本。PROPHET在周转肿瘤DNA（ctDNA）方面呈现出更高的敏感性，基线敏感性为45%。在预后分析中，PROPHET表现出超强的性能，并显示出平均领先时间为299天，能够准确预测复发。个性化非典型变异占总数的98.2%，其预后效应与典型变异相似。提出的肿瘤-淋巴结-转移-血液（TNMB）分级在术后判断辅助治疗预后时具有超越TNM分期的优势。PROPHET展示了评估辅助治疗效果和作为模糊的放射诊断的裁判的潜力。这些发现突显了个性化癌症技术在MRD检测方面的潜在优势。© 2023 Elsevier Inc. 发布。

We report a personalized tumor-informed technology, Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (PROPHET) using deep sequencing of 50 patient-specific variants to detect molecular residual disease (MRD) with a limit of detection of 0.004%. PROPHET and state-of-the-art fixed-panel assays were applied to 760 plasma samples from 181 prospectively enrolled early stage non-small cell lung cancer patients. PROPHET shows higher sensitivity of 45% at baseline with circulating tumor DNA (ctDNA). It outperforms fixed-panel assays in prognostic analysis and demonstrates a median lead-time of 299 days to radiologically confirmed recurrence. Personalized non-canonical variants account for 98.2% with prognostic effects similar to canonical variants. The proposed tumor-node-metastasis-blood (TNMB) classification surpasses TNM staging for prognostic prediction at the decision point of adjuvant treatment. PROPHET shows potential to evaluate the effect of adjuvant therapy and serve as an arbiter of the equivocal radiological diagnosis. These findings highlight the potential advantages of personalized cancer techniques in MRD detection.Copyright © 2023. Published by Elsevier Inc.