Arvind Dasari, MD, MS, The University of Texas MD Anderson Cancer Center, Houston, TX, talks on the use of circulating tumor DNA (ctDNA) to guide patient care. The use of ctDNA in cancer care ranges from early diagnosis to cancer screening. Dr Dasari explains how through observing changes in ctDNA levels across time during treatment for patients, ctDNA can aid in treatment decision making. However, this remains a challenge due to a current lack in the cut-offs for which level of ctDNA is considered a response versus progression. There are several ongoing clinical trials investigating the use of ctDNA for the early detection of cancers that are otherwise difficult to diagnose, such as biliary tract cancer (BTC) and pancreatic cancer (PC), that do not have current methods of screening and additionally for cancers such as breast and lung cancer where the screening methods used in clinical practice are faced with challenges, including cost, uptake and reliability. Furthermore, ctDNA can be utilized to detect minimal residual disease (MRD) in patients who have undergone surgery or other curative methods of treatment. Dr. Dasari explains that the detection of MRD is a highly powerful prognostic factor. Patients who are positive for MRD following curative treatment have a very high risk of recurrence and those who are negative for MRD have a substantially lower risk. The question is for patients who are MRD-negative, who per current guidelines would be receiving adjuvant chemotherapy, whether the intensity of therapy could be safely deescalated, reducing the associated unpleasant side effects. In the metastatic setting, ctDNA can be used for tumor profiling with fast results. Moreover, ctDNA can monitor resistance mechanisms in terms of targeted therapy, such as anti-EGFR in colorectal cancer (CRC), to then discern whether the resistance mechanism can be targeted with other targeted treatments and observe via the ctDNA if the cancer gets cleared from the mechanism of resistance to be able to subsequently rechallenge the tumor with anti-EGFR once again. Ongoing studies are attempting to establish the clinical utility of ctDNA to guide patient care, to ultimately improve patient outcomes. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2022.