Chakrabarti Sakti, Xie Hao, Urrutia Raul, Mahipal Amit
Department of Hematology-Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Department of Gastrointestinal Oncology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA.
Cancers (Basel). 2020 Sep 29;12(10):2808. doi: 10.3390/cancers12102808.
The current standard treatment for patients with early-stage colon cancer consists of surgical resection, followed by adjuvant therapy in a select group of patients deemed at risk of cancer recurrence. The decision to administer adjuvant therapy, intended to eradicate the clinically inapparent minimal residual disease (MRD) to achieve a cure, is guided by clinicopathologic characteristics of the tumor. However, the risk stratification based on clinicopathologic characteristics is imprecise and results in under or overtreatment in a substantial number of patients. Emerging research indicates that the circulating tumor DNA (ctDNA), a fraction of cell-free DNA (cfDNA) in the bloodstream that originates from the neoplastic cells and carry tumor-specific genomic alterations, is a promising surrogate marker of MRD. Several recent studies suggest that ctDNA-guided risk stratification for adjuvant therapy outperforms existing clinicopathologic prognostic indicators. Preliminary data also indicate that, aside from being a prognostic indicator, ctDNA can inform on the efficacy of adjuvant therapy, which is the underlying scientific rationale for several ongoing clinical trials evaluating ctDNA-guided therapy escalation or de-escalation. Furthermore, serial monitoring of ctDNA after completion of definitive therapy can potentially detect cancer recurrence much earlier than conventional surveillance methods that may provide a critical window of opportunity for additional curative-intent therapeutic interventions. This article presents a critical overview of published studies that evaluated the clinical utility of ctDNA in the management of patients with early-stage colon cancer, and discusses the potential of ctDNA to transform the adjuvant therapy strategies.
早期结肠癌患者目前的标准治疗包括手术切除，随后对部分被认为有癌症复发风险的患者进行辅助治疗。辅助治疗旨在根除临床上不明显的微小残留病灶（MRD）以实现治愈，其决策依据肿瘤的临床病理特征。然而，基于临床病理特征的风险分层并不精确，导致大量患者接受了不足或过度的治疗。新出现的研究表明，循环肿瘤DNA（ctDNA）是血液中游离DNA（cfDNA）的一部分，源自肿瘤细胞并携带肿瘤特异性基因组改变，是一种很有前景的MRD替代标志物。最近的几项研究表明，ctDNA指导的辅助治疗风险分层优于现有的临床病理预后指标。初步数据还表明，除了作为预后指标外，ctDNA还可以为辅助治疗的疗效提供信息，这是几项正在进行的评估ctDNA指导的治疗强化或降级的临床试验的潜在科学依据。此外，在确定性治疗完成后对ctDNA进行连续监测，可能比传统监测方法更早地检测到癌症复发，而传统监测方法可能为额外的根治性治疗干预提供关键的机会窗口。本文对已发表的评估ctDNA在早期结肠癌患者管理中的临床应用的研究进行了批判性综述，并讨论了ctDNA改变辅助治疗策略的潜力。
