研究动态
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液体活检在癌症外科患者中的应用:综述。

Applications of Liquid Biopsy for Surgical Patients With Cancer: A Review.

发表日期:2023 Nov 01
作者: Kelly M Mahuron, Yuman Fong
来源: Cellular & Molecular Immunology

摘要:

液体活检是一种新兴工具,有可能改变肿瘤护理实践。对于手术患者来说,其最佳临床应用目前尚未确定。循环肿瘤细胞 (CTC) 和循环肿瘤 DNA (ctDNA) 等液体活检分析物是临床研究最多的检测方法,最初仅限于晚期疾病。在转移情况下,CTC 和 ctDNA 水平具有预后意义。尽管它们的水平与治疗反应相关,但 CTC 指导下的无反应者全身治疗方案转换尚未被证明可以改善临床结果。 ctDNA 基因组分析已取得成功,目前美国食品和药物管理局批准了多种基于血浆的检测方法,可以检测可操作的突变以指导全身治疗。检测灵敏度方面的技术进步将 ctDNA 的用途扩大到早期和可切除疾病,从而可以检测微小残留疾病。术后 ctDNA 水平是疾病复发的有力预测因子,ctDNA 检测通常先于血清癌胚抗原升高和放射学变化。然而,尚未证明其用于监测可以改善临床结果。 ctDNA 的一个有前景的应用是辅助治疗的升级和降级。一项 2 期临床试验表明,对于高危 II 期结直肠癌且术后 ctDNA 阴性的患者,降级治疗与接受标准护理化疗的患者具有相似的无复发生存率。这些结果表明,ctDNA 可能有助于选择将从辅助化疗中受益的患者,多项临床试验正在积极进行中。尽管液体活检的最佳使用仍存在不确定性,但它有可能显着改善对各个阶段癌症患者的护理的疾病。外科医生了解如何使用和解释这些检测至关重要,他们应该积极参与临床试验以推进该领域的发展。
Liquid biopsy is an emerging tool with the potential to change oncologic care practices. Optimal clinical applications for its use are currently undefined for surgical patients.Liquid biopsy analytes such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been the most clinically studied assays and were initially limited to advanced-stage disease. In the metastatic setting, CTCs and ctDNA levels are prognostic. Although their levels correlate with treatment response, CTC-guided systemic regimen switches for nonresponders have not been shown to improve clinical outcomes. ctDNA genomic profiling has succeeded, and there are now multiple plasma-based assays approved by the US Food and Drug Administration that can detect actionable mutations to guide systemic therapy. Technological advancements in assay sensitivity have expanded the use of ctDNA to early-stage and resectable disease, allowing for detection of minimal residual disease. Postoperative ctDNA levels are a strong predictor of disease recurrence, and ctDNA detection often precedes serum carcinoembryonic antigen elevation and radiographic changes. However, its use for surveillance has not been shown to improve clinical outcomes. A promising application of ctDNA is for adjuvant therapy escalation and de-escalation. A phase 2 clinical trial demonstrated that treatment de-escalation for patients with high-risk stage II colorectal cancer and negative postoperative ctDNA had similar recurrence-free survival as patients receiving standard-of-care chemotherapy. These results suggest that ctDNA may help select patients who will benefit from adjuvant chemotherapy, and multiple clinical trials are actively underway.Although uncertainties regarding the optimal use of liquid biopsy remain, it has the potential to significantly improve care for patients with cancer at all stages of disease. It is critical that surgeons understand how to use and interpret these assays, and they should be active participants in clinical trials to advance the field.