MRD / ctDNA / DTP — 从检测到治疗决策
肿瘤知情检测：先给原发瘤做测序，再在血浆里追这组突变，灵敏度可以到万分之一以下。Tie 在全体会议上把路标钉在百万分之一。CheckMate 77T 用的就是这条：纳武利尤单抗组清除 75% 对安慰剂 46%。
液体活检的潜力早已被反复申说。2017年的综述系统梳理了循环肿瘤DNA（ctDNA）在预后判断、分子分型与疗效监测上的转化前景，但彼时领域仍处在从原理验证迈向临床应用的过渡期，对游离DNA生物学的认识也远未完整[1]。此后，应用场景被进一步细分为癌症检测、预后预测、治疗监测，以及基于治疗靶点或耐药机制的患者分层[5]；CAPP-Seq等深度测序技术日趋成熟，连续采样甚至被用于区分免疫检查点抑制的独特反应模式[4]。可是在非小细胞肺癌（NSCLC）实践中，指南已按可靶向突变为转移性疾病选择精准治疗[2]，血液检测多被定位为诊断与分型的入口——系列血浆检测能否实时改写治疗决策，长期缺乏大样本证据。
AACR 2026年会上，约翰霍普金斯团队（@ValsamoA与William Bowers）报告的工作正对准这一卡点：液体活检的价值“超越了单纯诊断”，系列血浆全面基因组分析（pCGP）正在实时重塑NSCLC的管理，其中36%的初治患者携带可干预的分子变异。与该工作对应的研究已通过同行评审发表，是一项纳入718例接受pCGP的NSCLC患者的回顾性分析，主题正是捕获治疗耐药并指导管理[6]。
放回上述脉络，其推进在于把“应用清单”落到了大样本临床：耐药机制监测与据此分层，本就是液体活检被寄予厚望却难以铺开的方向[5]；血液基因面板此前也多在单一具体问题上验证，例如血检肿瘤突变负荷预测免疫治疗疗效[3]。系列pCGP则贯穿治疗全程、直接对接管理决策，且初治阶段36%的可干预检出率，与NSCLC现行“按可靶向突变选药”的框架[2]相呼应。据报道，该研究还专门刻画了EGFR突变NSCLC在pCGP下的突变图谱[7]。
克制仍是必要的：原帖在“36%的可干预……”处戛然而止，后续结论无从看到；研究为回顾性设计[6]，“实时改变管理”距前瞻性验证的结局改善尚有距离；游离DNA生物学的未知[1]与检测敏感性、特异性的现实约束[5]也依旧横亘在前。pCGP能否从“看见耐药”走到“证明改写生存”，是下一道必答题。
- 1.Liquid biopsies come of age: towards implementation of circulating tumour DNA · Nat Rev Cancer 2017
- 2.Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology · J Natl Compr Canc Netw 2022
- 3.Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Patients With Non-Small Cell Lung Cancer With Use of a Next-Generation Sequencing Cancer Gene Panel · JAMA Oncol 2019
- 4.Liquid biopsy: current technology and clinical applications · J Hematol Oncol 2022
- 5.Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy · Cancer Discov 2016
- 6.Serial Plasma Comprehensive Genomic Profiling Captures ... · aacrjournals.org 2026
- 7.Aliyah Pabani from Johns Hopkins University · scilit.com 2026
A troubling trend in early phase #NSCLC clinical trials.
Today new LUNGevity research at #AACR26 shows that smaller clinical trial sites in community & rural settings are declining--limiting patient access to lung cancer care. Download the research:
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Andrew R. Conery, Daniel S. La, Artyom A. Alekseyenko, David Marcoux, Aaron G. Bart, Matt L. Harlow, Patrick R. Arsenault, Nico R. Cantone, Rebecca L. Casaubon, Hari B. Kamadurai, Aravind Prasad Medikonda, Duncan E. Nunes, Tim J. Wigle, Maolin Yu, Aleksandra Zagulyaeva, Christine Zarate, Kathleen I. Seyb, Patrick Trojer, Vito J. Palombella
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