Clinical utility of circulating tumor DNA as a response and follow-up marker in cancer therapy
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CLINICAL
Clinical utility of circulating tumor DNA as a response and follow-up marker in cancer therapy Pieter A. Boonstra 1 & Thijs T. Wind 1 & Michel van Kruchten 1 & Ed Schuuring 2 & Geke A. P. Hospers 1 & Anthonie J. van der Wekken 3 & Derk-Jan de Groot 1 & Carolien P. Schröder 1 & Rudolf S. N. Fehrmann 1 & Anna K. L. Reyners 1
# The Author(s) 2020
Abstract Response evaluation for cancer treatment consists primarily of clinical and radiological assessments. In addition, a limited number of serum biomarkers that assess treatment response are available for a small subset of malignancies. Through recent technological innovations, new methods for measuring tumor burden and treatment response are becoming available. By utilization of highly sensitive techniques, tumor-specific mutations in circulating DNA can be detected and circulating tumor DNA (ctDNA) can be quantified. These so-called liquid biopsies provide both molecular information about the genomic composition of the tumor and opportunities to evaluate tumor response during therapy. Quantification of tumor-specific mutations in plasma correlates well with tumor burden. Moreover, with liquid biopsies, it is also possible to detect mutations causing secondary resistance during treatment. This review focuses on the clinical utility of ctDNA as a response and follow-up marker in patients with non-small cell lung cancer, melanoma, colorectal cancer, and breast cancer. Relevant studies were retrieved from a literature search using PubMed database. An overview of the available literature is provided and the relevance of ctDNA as a response marker in anti-cancer therapy for clinical practice is discussed. We conclude that the use of plasma-derived ctDNA is a promising tool for treatment decision-making based on predictive testing, detection of resistance mechanisms, and monitoring tumor response. Necessary steps for translation to daily practice and future perspectives are discussed. Keywords ctDNA . Mutation detection . Therapy monitoring . Follow-up . Driver mutations
1 Introduction Response evaluation during anti-cancer therapy and follow-up of patients with solid malignancies is currently primarily based on radiological assessments according to response evaluation criteria in solid tumors (RECIST) [1]. Repeated
Pieter A. Boonstra and Thijs T. Wind contributed equally to this work. * Anna K. L. Reyners [email protected] 1
Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
2
Department of Pathology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
3
Department of Pulmonary Medicine, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
radiologic assessments are however time consuming, costly, and increase the radiation burden for the patient. This is especially an issue in the context of the increasing number of longterm cancer survivors due
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