在正在进行的针对靶向治疗药物及其临床应用的研究中，结合基因组学和蛋白质组学的研究，探索了多种用于肺癌治疗的新方法，并基于特定可操作的基因突变定义了“分子亚型”。液体活检，包括循环肿瘤DNA（ctDNA）测试，对于肿瘤诊断和全基因组分析（例如鉴定癌症亚型和癌细胞的主要遗传改变）具有重要价值。本报告描述了一例66岁的男性患者，初诊为驱动基因突变阴性的晚期非小细胞肺癌（NSCLC），在接受传统治疗过程中。该患者进行了定期监测，包括持续的ctDNA分析、影像学检查和肿瘤标志物水平评估，如癌胚抗原（CEA）。患者最初表现为双下肢深静脉血栓形成，肺部无任何症状，正电子发射计算机断层扫描显示右下肺叶不规则结节和肿大的右锁骨上淋巴结。随后的超声引导下针吸活检指示侵袭性不能手术治疗的ⅡIC段疾病，基于美国癌症联合委员会的肿瘤-淋巴结-转移分期系统。肿瘤组织和外周血的下一代测序证实了驱动基因突变阴性基因，包括表皮生长因子受体、大鼠肉瘤、ALK受体酪氨酸激酶、ROS1原癌基因受体酪氨酸激酶和转录过程中的重排（RET）基因。经过5年的化疗放疗和ctDNA及CEA水平的监测，检测到的KIF5B-RET融合物于ctDNA和升高的CEA水平促使早期扫描，发现疾病进展。随后患者接受了口服RET抑制剂pralsetinib，已经接受了≥17个月的治疗，无法检测到KIF5B-RET ctDNA或升高的CEA水平，以及基于实体肿瘤反应评价标准v1.1的影像学结果表明持续部分缓解和稳定疾病。本病例说明了在治疗过程中的肿瘤生物标志物监测作为一种非创伤性方法，用于评估治疗反应和早期疾病进展的潜在作用，对晚期NSCLC患者。将循环肿瘤生物标志物测试整合到晚期NSCLC患者的管理中需要进一步的前瞻性研究来积极评估和阐明最佳治疗策略。版权所有：Bi等。

Ongoing investigations of targeted therapeutic agents and their increased clinical applications, together with research in genomics and proteomics, have explored a variety of novel approaches for treatment of lung cancer, and 'molecular subtypes' have been defined based on specific actionable genetic aberrations. Liquid biopsies, including circulating tumor DNA (ctDNA) testing, are of value for cancer diagnosis and comprehensive genomic profiling, such as the identification of cancer subtypes and major genetic alterations in cancer cells. The case of a 66-year-old male patient with newly-diagnosed driver mutation-negative advanced non-small cell lung cancer (NSCLC) who underwent conventional therapy is described in the present report. The patient underwent regular monitoring, including continuous ctDNA analysis, imaging and assessment of tumor marker levels such as carcinoembryonic antigen (CEA). The patient initially presented with deep vein thrombosis which affected both lower extremities and without any symptoms in the lung, with a positron emission tomography scan identifying irregular pulmonary nodules in the right lower lobe and enlarged right supraclavicular lymph nodes. Subsequent ultrasound-guided fine-needle aspiration with nodule biopsy indicated advanced unresectable disease at stage IIIB based on the Tumor-Node-Metastasis staging system by the American Joint Committee on Cancer. Next-generation sequencing of tumor tissue and peripheral blood confirmed driver mutation-negative genes, including epidermal growth factor receptor, rat sarcoma, ALK receptor tyrosine kinase, ROS1 proto-oncogene receptor tyrosine kinase and rearrangement during transfection (RET). After 5 years of chemoradiotherapy and surveillance of ctDNA and CEA levels, detectable kinesin family member 5B (KIF5B)-RET fusion in ctDNA and rising CEA levels prompted early scans, which identified disease progression. The patient subsequently received the oral RET inhibitor pralsetinib, with treatment being currently ongoing for ≥17 months without detectable KIF5B-RET ctDNA or elevated CEA levels, with an ongoing minor response and stable disease based on Response Evaluation Criteria in Solid Tumors v1.1 on imaging. The present case illustrates the potential role of on-therapy circulating tumor biomarker monitoring as a non-traumatic method to evaluate therapy response and detect early disease progression in patients with advanced NSCLC. Integration of circulating tumor biomarker testing into the management of patients with advanced NSCLC requires additional prospective studies to actively assess and elucidate optimal treatment strategies.Copyright: © Bi et al.