切换至 "中华医学电子期刊资源库"

中华诊断学电子杂志 ›› 2025, Vol. 13 ›› Issue (04) : 236 -241. doi: 10.3877/cma.j.issn.2095-655X.2025.04.004

生物医学技术

液体活检驱动下实体瘤微小残留病灶"监测—干预"闭环管理的构建与实践
王雪星1, 孙凯2, 唐星星3, 周国忠1,()   
  1. 1650399 昆明理工大学附属安宁市第一人民医院肿瘤科
    2341000 赣州市肿瘤医院肿瘤中心
    3661000 个旧,红河州第三人民医院(红河州肿瘤医院)胸外科
  • 收稿日期:2025-09-06 出版日期:2025-11-26
  • 通信作者: 周国忠

Establishing and implementing a closed-loop management system for monitoring and intervening in minimal residual disease in solid tumors driven by liquid biopsy

Xuexing Wang1, Kai Sun2, Xingxing Tang3, Guozhong Zhou1,()   

  1. 1Department of Oncology, Anning First People′s Hospital Affiliated to Kunming University of Science and Technology, Anning 650399, China
    2Oncology Center, Ganzhou Cancer Hospital, Ganzhou 341000, China
    3Department of Thoracic Surgery, Honghe Prefecture Third People′s Hospital (Honghe Prefecture Cancer Hospital), Gejiu 661000, China
  • Received:2025-09-06 Published:2025-11-26
  • Corresponding author: Guozhong Zhou
引用本文:

王雪星, 孙凯, 唐星星, 周国忠. 液体活检驱动下实体瘤微小残留病灶"监测—干预"闭环管理的构建与实践[J/OL]. 中华诊断学电子杂志, 2025, 13(04): 236-241.

Xuexing Wang, Kai Sun, Xingxing Tang, Guozhong Zhou. Establishing and implementing a closed-loop management system for monitoring and intervening in minimal residual disease in solid tumors driven by liquid biopsy[J/OL]. Chinese Journal of Diagnostics(Electronic Edition), 2025, 13(04): 236-241.

实体恶性肿瘤根治性治疗后复发和转移是导致患者死亡的主要原因之一,其主要原因在于体内残留着临床上难以检测出的微小残留病灶(MRD)。传统影像学检查和血清学标志物存在敏感度和特异度不足等缺点,导致临床治疗往往处于被动等待状态。近年来,随着循环肿瘤DNA(ctDNA)液体活检技术的快速发展,其具有高敏感度和实时动态监测的优点,使得MRD的精准检测被广泛关注。因此,本文整合了术后MRD基线监测、复发风险分层、动态预警、治疗干预决策和疗效动态评估等一系列过程,并提出一种基于液体活检的实体瘤"监测—干预"闭环管理模式,且进一步剖析该模式的核心技术平台,重点讨论不同ctDNA检测方案的优劣,此外以结直肠癌和肺癌等关键癌种为例,全面分析该模式在临床应用中的证据基础、现存争议和挑战,并对未来临床实践中关键技术、临床证据、经济效益评估和智能决策等方面进行前瞻性探讨,最终实现恶性实体肿瘤的个性化、动态化和前瞻性精准治疗。

Recurrence and metastasis remain the main causes of mortality in patients with solid tumors after curative treatment, largely driven by clinically undetectable minimal residual disease (MRD). Conventional imaging and serum biomarkers lack sufficient sensitivity and specificity for MRD detection, leading to delayed or passive clinical decision-making. Advances in circulating tumor DNA (ctDNA)-based liquid biopsy technology now enable highly sensitive and real-time monitoring of MRD.This study proposes a ctDNA-guided " monitoring-intervention" closed-loop clinical management model for solid tumors. The model integrates sequential processes encompassing postoperative MRD baseline assessment, recurrence risk stratification, early molecular warning, therapeutic intervention selection, and longitudinal efficacy evaluation. We analyze the core technological platforms supporting this framework, compare the strengths and limitations of different ctDNA detection strategies and outline system architecture and implementation approaches for the closed-loop model.Using colorectal and lung cancers as representative examples, this paper comprehensively reviews the supporting clinical evidence, ongoing controversies, and major challenges in translating this model into clinical practice. Furthermore, we provide forward-looking perspectives on standardizing key technologies, enriching clinical data, assessing cost-effectiveness, and developing intelligent decision-making systems to enable personalized, dynamic, and prospective precision treatment for solid malignancies.

图1 液体活检驱动的实体瘤"监测—干预"闭环管理模式注:A:患者在接受根治性治疗(如手术)后约4周,进行首次ctDNA基线检测;B:根据基线ctDNA状态进行风险分层。ctDNA阴性者被视为低复发风险,可考虑辅助治疗降级或直接进入监测期。ctDNA阳性者则为高复发风险,应考虑启动或升级辅助治疗;C:患者进入连续监测期,定期(如每3~6个月)检测ctDNA。ctDNA持续阴性提示疾病控制良好。若ctDNA由阴转阳,则构成"分子复发",是启动干预的关键预警信号,此时通常早于影像学复发;D:确认分子复发后,启动个体化的抢先治疗。治疗期间,通过监测ctDNA水平的动态变化来评估疗效。ctDNA水平下降或转阴提示治疗有效;若持续阳性或升高,则提示耐药,需调整方案;E:治疗成功后,患者再次进入动态监测循环,形成一个持续优化、主动管理的闭环;ctDNA为循环肿瘤DNA
[1]
Hu XLuo BQiu L,et al.Dezocine has the potential to regulate the clinical and biological features of tumors[J].Drug Des Devel Ther2022(16):1121-1129.DOI:10.2147/DDDT.S356863.
[2]
Liu YLi QChen T,et al.Clinical verification of vimentin/EpCAM immunolipid magnetic sorting system in monitoring CTCs in arterial and venous blood of advanced tumor[J].J Nanobiotechnology202119(1):185.DOI:10.1186/s12951-021-00929-x.
[3]
Homma MKKiko YHashimoto Y,et al.Intracellular localization of CK2α as a prognostic factor in invasive breast carcinomas[J].Cancer Sci2021112(2):619-628.DOI:10.1111/cas.14728.
[4]
López-Ruiz JAMieza JAZabalza I,et al.Comparison of genomic profiling data with clinical parameters:implications for breast cancer prognosis[J].Cancers (Basel)202214(17):4197.DOI:10.3390/cancers14174197.
[5]
Moding EJ, Nabet BY, Alizadeh AA, et al. Detecting liquid remnants of solid tumors:circulating tumor DNA minimal residual disease[J].Cancer Discov202111(12):2968-2986.DOI:10.1158/2159-8290.CD-21-0634.
[6]
Tarasiuk AMackiewicz TMałecka-Panas E,et al.Biomarkers for early detection of pancreatic cancer - miRNAs as a potential diagnostic and therapeutic tool?[J].Cancer Biol Ther202122(5-6):347-356.DOI:10.1080/15384047.2021.1941584.
[7]
Duffy MJLamerz RHaglund C,et al.Tumor markers in colorectal cancer,gastric cancer and gastrointestinal stromal cancers:european group on tumor markers 2014 guidelines update[J].Int J Cancer2014134(11):2513-2522.DOI:10.1002/ijc.28384.
[8]
Heitzer EHaque ISRoberts C,et al.Current and future perspectives of liquid biopsies in genomics-driven oncology[J].Nat Rev Genet201920(2):71-88.DOI:10.1038/s41576-018-0071-5.
[9]
Schraa SJvan Rooijen KLKoopman M,et al.Cell-free circulating (tumor) DNA before surgery as a prognostic factor in non-metastatic colorectal cancer:a systematic review[J].Cancers (Basel)202214(9):2218.DOI:10.3390/cancers14092218.
[10]
Wang RZhao ACao N,et al.The value of circulation tumor DNA in predicting postoperative recurrence of colorectal cancer:a meta-analysis[J].Int J Colorectal Dis202035(8):1463-1475.DOI:10.1007/s00384-020-03667-y.
[11]
Chen YMo SWu M,et al.Circulating tumor DNA as a prognostic indicator of colorectal cancer recurrence-a systematic review and meta-analysis[J].Int J Colorectal Dis202237(5):1021-1027.DOI:10.1007/s00384-022-04144-4.
[12]
Henriksen TVTarazona NFrydendahl A,et al.Circulating tumor DNA in stage Ⅲ colorectal cancer,beyond minimal residual disease detection,toward assessment of adjuvant therapy efficacy and clinical behavior of recurrences[J].Clin Cancer Res202228(3):507-517.DOI:10.1158/1078-0432.CCR-21-2404.
[13]
Fu RHuang JTian X,et al.Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer:results from a multicenter study[J].Mol Oncol202317(5):825-838.DOI:10.1002/1878-0261.13387.
[14]
Raunkilde LHansen TFAndersen RF,et al.NPY Gene methylation in circulating tumor DNA as an early biomarker for treatment effect in metastatic colorectal cancer[J].Cancers (Basel)202214(18):4459.DOI:10.3390/cancers14184459.
[15]
Malla MLoree JMKasi PM,et al.Using circulating tumor DNA in colorectal cancer:current and evolving practices[J].J Clin Oncol202240(24):2846-2857.DOI:10.1200/JCO.21.02615.
[16]
Azzi GTavallai MAushev VN, et al. Using tumor-informed circulating tumor DNA (ctDNA)-based testing for patients with anal squamous cell carcinoma[J].ONCOLOGIST202328 (3):220-229.DOI:10.1093/oncolo/oyac249.
[17]
Coombes RCPage KSalari R,et al.Personalized detection of circulating tumor dna antedates breast cancer metastatic recurrence[J].Clin Cancer Res201925(14):4255-4263.DOI:10.1158/1078-0432.CCR-18-3663.
[18]
Hua XZhou HWu HC,et al.Tumor detection by analysis of both symmetric- and hemi-methylation of plasma cell-free DNA[J].Nat Commun202415(1):6113.DOI:10.1038/s41467-024-50471-1.
[19]
Cristiano SLeal APhallen J,et al.Genome-wide cell-free DNA fragmentation in patients with cancer[J].Nature2019570(7761):385-389.DOI:10.1038/s41586-019-1272-6.
[20]
Li YJiang GWu W,et al.Multi-omics integrated circulating cell-free DNA genomic signatures enhanced the diagnostic performance of early-stage lung cancer and postoperative minimal residual disease[J].EBioMedicine2023(91):104553.DOI:10.1016/j.ebiom.2023.104553.
[21]
Tie JCohen JWang YX,et al.The potential of circulating tumor DNA (ctDNA) to guide adjuvant chemotherapy decision making in locally advanced rectal cancer (LARC)[J].J CLIN ONCOL201735 (15_suppl):3521-3521.DOI:10.1200/jco.2017.35.15_suppl.3521.
[22]
Chaudhuri AA, Chabon JJ, Lovejoy AF, et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling[J].Cancer Discov20177(12):1394-1403.DOI:10.1158/2159-8290.CD-17-0716.
[23]
Zhong RGao RFu W,et al.Accuracy of minimal residual disease detection by circulating tumor DNA profiling in lung cancer:a meta-analysis[J].BMC Med202321(1):180.DOI:10.1186/s12916-023-02849-z.
[24]
Magbanua MSwigart LBWu HT,et al.Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival[J].Ann Oncol202132(2):229-239.DOI:10.1016/j.annonc.2020.11.007.
[25]
Birkenkamp-Demtröder KChristensen ENordentoft I,et al.Monitoring treatment response and metastatic relapse in advanced bladder cancer by liquid biopsy analysis[J].Eur Urol201873(4):535-540.DOI:10.1016/j.eururo.2017.09.011.
[26]
Phallen JSausen MAdleff V,et al.Direct detection of early-stage cancers using circulating tumor DNA[J].Sci Transl Med20179(403):eaan2415.DOI:10.1126/scitranslmed.aan2415.
[27]
Wang YLi LCohen JD,et al.Prognostic potential of circulating tumor DNA measurement in postoperative surveillance of nonmetastatic colorectal cancer[J].JAMA Oncol20195(8):1118-1123.DOI:10.1001/jamaoncol.2019.0512.
[28]
Taniguchi HNakamura YKotani D,et al.CIRCULATE-Japan:circulating tumor DNA-guided adaptive platform trials to refine adjuvant therapy for colorectal cancer[J].Cancer Sci2021112(7):2915-2920.DOI:10.1111/cas.14926.
[29]
Tie JCohen JDLahouel K,et al.Circulating tumor dna analysis guiding adjuvant therapy in stage Ⅱ colon cancer[J].N Engl J Med2022386(24):2261-2272.DOI:10.1056/NEJMoa2200075.
[30]
Tsuboi MHerbst RSJohn T,et al.Overall survival with osimertinib in resected EGFR-mutated NSCLC[J].N Engl J Med2023389(2):137-147.DOI:10.1056/NEJMoa2304594.
[31]
Herbst RSJohn TGrohé C,et al.Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage ⅠB-ⅢA non-small-cell lung cancer[J].Nat Med202531(6):1958-1968.DOI:10.1038/s41591-025-03577-y.
[32]
Felip EAltorki NZhou C,et al.Adjuvant atezolizumab after adjuvant chemotherapy in resected stage ⅠB-ⅢA non-small-cell lung cancer (IMpower010):a randomised,multicentre,open-label,phase 3 trial[J].Lancet2021398(10308):1344-1357.DOI:10.1016/S0140-6736(21)02098-5.
[33]
Sugimoto AMatsumoto SUdagawa H,et al.A large-scale prospective concordance study of plasma- and tissue-based next-generation targeted sequencing for advanced non-small cell lung cancer (LC-SCRUM-Liquid)[J].Clin Cancer Res202329(8):1506-1514.DOI:10.1158/1078-0432.CCR-22-1749.
[34]
Stadler JCBelloum YDeitert B,et al.Current and future clinical applications of ctDNA in Immuno-Oncology[J].Cancer Res202282(3):349-358.DOI:10.1158/0008-5472.CAN-21-1718.
[35]
Powles TAssaf ZJDavarpanah N,et al.ctDNA guiding adjuvant immunotherapy in urothelial carcinoma[J].Nature2021595(7867):432-437.DOI:10.1038/s41586-021-03642-9.
[36]
Turner NCSwift CJenkins B,et al.Results of the c-TRAK TN trial:a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer[J].Ann Oncol202334(2):200-211.DOI:10.1016/j.annonc.2022.11.005.
[37]
Lee JHLong GVBoyd S,et al.Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma[J].Ann Oncol201728(5):1130-1136.DOI:10.1093/annonc/mdx026.
[38]
Chan WY, Lee JH, Stewart A, et al. Circulating tumour DNA dynamics predict recurrence in stage Ⅲ melanoma patients receiving neoadjuvant immunotherapy[J].J Exp Clin Cancer Res202443(1):238.DOI:10.1186/s13046-024-03153-1.
[39]
Loeffler CBando HSainath S,et al.HIBRID:histology-based risk-stratification with deep learning and ctDNA in colorectal cancer[J].Nat Commun202516(1):7561.DOI:10.1038/s41467-025-62910-8.
[40]
Volinsky-Fremond S, Horeweg N, Andani S, et al. Prediction of recurrence risk in endometrial cancer with multimodal deep learning[J].Nat Med202430(7):1962-1973.DOI:10.1038/s41591-024-02993-w.
[41]
Dhaliwal AZandu MKhurana S,et al.Anti CD19 CAR-T cell therapy can clear minimal residual disease in bone marrow of patients with relapsed or refractory B cell non-hodgkin′s lymphomas[J].BLOOD2022140 (Supple 1):12760-12761.DOI:10.1182/blood-2022-170620.
[42]
Kasi ADiaz FAl-Rajabi RMT,et al.Targeting minimal residual disease (MRD) in resected RAS mutated pancreatic cancer with vaccine TG01/QS-21 +/- PD-1 inhibitor,balstilimab:a randomized phase II study (TESLA)[J].J Clin Oncol202341 (16_suppl):TPS4205-TPS4205.DOI:10.1200/jco.2023.41.16_suppl.tps4205.
[1] 郭健冉, 解磐磐, 王松, 谭明真, 付波. 特异性DNA 甲基化位点在乳腺癌中的研究进展[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 49-53.
[2] 李瑞芳, 王明帅, 邢念增. 循环肿瘤细胞在膀胱癌诊断和预后中的应用进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(06): 705-713.
[3] 胡博文, 胡亚兰, 梁辉. 前列腺癌早期筛查的常见方法及最新研究进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(06): 800-808.
[4] 杨硕, 郭佳. 液体活检在前列腺癌进展监测中的研究进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(05): 558-564.
[5] 刘学飞, 赵东, 李婷婷, 李佳浓, 葛亚楠, 李博. RB1基因状态对非小细胞肺癌免疫检查点抑制剂联合化疗反应的意义[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(04): 580-585.
[6] 乔鲜丽, 田向阳, 周文雅, 秦泽敏, 郭姗姗, 于俊岩. 循环肿瘤DNA 对非小细胞肺癌术后复发风险的预测意义[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(03): 395-400.
[7] 王夏, 袁高峰, 卞光利, 贾会军, 韩光, 宋震, 曹主根. 循环肿瘤DNA 预测非小细胞肺癌辅助化疗后复发风险的临床意义[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(02): 266-272.
[8] 赵海燕, 靳海涛, 孔莺, 何瑞远. 血浆NGS-ctDNA对EGFR-TKIs治疗晚期NSCLC患者的预后意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(03): 385-391.
[9] 郑大雯, 王健东. 胆囊癌辅助诊断研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 769-773.
[10] 杨智義, 赵成俊, 胡欣芫, 潘佰猛, 张秋雨, 张挽乾, 曹芮, 张灵强. 外周血cfDNA液体活检技术在肝棘球蚴病诊治中的应用进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 389-393.
[11] 马欢欢, 马晨辉, 邓小博, 王博方, 何普毅, 王云鹏, 许博, 俞荣, 王娜, 陈昊. 肝癌实体瘤治疗疗效评价系统的研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 377-383.
[12] 张占国. 靶向免疫治疗时代的肝癌肝切除术再思考[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 11-15.
[13] 赵迪, 杨鑫鑫, 孟宏学. 液体活检技术在结直肠癌诊疗领域的应用[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(02): 135-140.
[14] 顾睿祈, 方洪生, 蔡国响. 循环肿瘤DNA检测在结直肠癌诊治中的应用与进展[J/OL]. 中华结直肠疾病电子杂志, 2023, 12(06): 453-459.
[15] 孙晗, 于冰, 武侠, 周熙朗. 基于循环肿瘤DNA 甲基化的结直肠癌筛查预测模型的构建与验证[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 500-506.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?