The Promise of Circulating Tumor DNA (ctDNA) in the Management of Early-Stage Colon Cancer: A Critical Review.
The Promise of Circulating Tumor DNA (ctDNA) in the Management of Early-Stage Colon Cancer: A Critical Review.
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DOI：
10.3390/cancers12102808
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发表时间：
2020-09-29
期刊：
影响因子：
5.2
通讯作者：
Mahipal A
中科院分区：
文献类型：
--
作者：
Chakrabarti S;Xie H;Urrutia R;Mahipal A
目前，对局限性结肠癌的治疗包括手术，如果怀疑存在残留的癌细胞，则在手术后进行化疗。然而，目前用于确定手术后是否存在残留癌症的标准工具并不准确，这导致了相当数量的患者治疗不足或过度。新出现的研究表明，循环肿瘤DNA(CtDNA)可以比目前可用的工具更精确地揭示手术后肿瘤残留的存在，并有助于术后是否需要化疗的治疗决策。此外，ctDNA可能有助于确定化疗的有效性，并比目前的标准工具更早地检测癌症复发。在这篇综述中，我们对现有数据进行了严格的评估，为读者提供了一个关于ctDNA如何在不久的将来潜在地改变局限性结肠癌治疗的概述。目前对早期结肠癌患者的标准治疗包括手术切除，然后对一组被认为有癌症复发风险的患者进行辅助治疗。实施辅助治疗的决定，旨在根除临床上看不见的微小残留病(MRD)以实现治愈，这是由肿瘤的临床病理特征指导的。然而，基于临床病理特征的风险分层是不准确的，并导致相当数量的患者治疗不足或过度。新近的研究表明，循环肿瘤DNA(CtDNA)是血液中源于肿瘤细胞并携带肿瘤特异性基因组改变的一部分无细胞DNA(CfDNA)，是一种有前景的MRD替代标志物。最近的几项研究表明，ctDNA引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，除了是一种预后指标外，ctDNA还可以告知辅助治疗的疗效，这是正在进行的几项临床试验评估ctDNA引导的治疗升级或降级的基本科学原理。此外，在最终治疗完成后，连续监测ctDNA可能比传统监测方法更早地发现癌症复发，这可能为更多的治疗意图治疗干预提供关键的机会之窗。本文对已发表的评价ctDNA在早期结肠癌患者治疗中的临床应用，以及ctDNA改变辅助治疗策略的潜力的研究进行了重要的综述。
Currently, the treatment for localized colon cancer consists of surgery and, if the presence of residual cancer cells is suspected, chemotherapy following the surgery. However, the current standard tools to determine the presence of residual cancer after the surgery are imprecise, which results in under- or overtreatment in a significant number of patients. Emerging research indicates that circulating tumor DNA (ctDNA) can reveal the presence of residual cancer after surgery with much higher precision than the presently available tools, and can help with the treatment decision regarding a need for chemotherapy after the surgery. Furthermore, ctDNA can potentially help determine the effectiveness of chemotherapy and detect cancer recurrence much earlier than the current standard tools. In this review, we have critically evaluated available data to provide the readers with an overview of how ctDNA can potentially transform the treatment of localized colon cancer in the near future. 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 the potential of ctDNA to transform the adjuvant therapy strategies.
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影响因子：
9.3
作者：
Chan, K. C. Allen;Jiang, Peiyong;Lo, Y. M. D.
通讯作者：
Lo, Y. M. D.
DOI：
10.1056/nejmoa1713709
发表时间：
2018-03-29
期刊：
The New England journal of medicine
影响因子：
--
作者：
Grothey A;Sobrero AF;Shields AF;Yoshino T;Paul J;Taieb J;Souglakos J;Shi Q;Kerr R;Labianca R;Meyerhardt JA;Vernerey D;Yamanaka T;Boukovinas I;Meyers JP;Renfro LA;Niedzwiecki D;Watanabe T;Torri V;Saunders M;Sargent DJ;Andre T;Iveson T
通讯作者：
Iveson T
影响因子：
78.8
作者：
Abbosh, Christopher;Birkbak, Nicolai J.;Swanton, Charles
通讯作者：
Swanton, Charles
影响因子：
7.4
作者：
Hindson, Benjamin J.;Ness, Kevin D.;Masquelier, Donald A.;Belgrader, Phillip;Heredia, Nicholas J.;Makarewicz, Anthony J.;Bright, Isaac J.;Lucero, Michael Y.;Hiddessen, Amy L.;Legler, Tina C.;Kitano, Tyler K.;Hodel, Michael R.;Petersen, Jonathan F.;Wyatt, Paul W.;Steenblock, Erin R.;Shah, Pallavi H.;Bousse, Luc J.;Troup, Camille B.;Mellen, Jeffrey C.;Wittmann, Dean K.;Erndt, Nicholas G.;Cauley, Thomas H.;Koehler, Ryan T.;So, Austin P.;Dube, Simant;Rose, Klint A.;Montesclaros, Luz;Wang, Shenglong;Stumbo, David P.;Hodges, Shawn P.;Romine, Steven;Milanovich, Fred P.;White, Helen E.;Regan, John F.;Karlin-Neumann, George A.;Hindson, Christopher M.;Saxonov, Serge;Colston, Bill W.
通讯作者：
Colston, Bill W.
影响因子：
3.7
作者：
Gale D;Lawson ARJ;Howarth K;Madi M;Durham B;Smalley S;Calaway J;Blais S;Jones G;Clark J;Dimitrov P;Pugh M;Woodhouse S;Epstein M;Fernandez-Gonzalez A;Whale AS;Huggett JF;Foy CA;Jones GM;Raveh-Amit H;Schmitt K;Devonshire A;Green E;Forshew T;Plagnol V;Rosenfeld N
通讯作者：
Rosenfeld N