Drs. Shaalan Beg and Aparna Parikh discuss the role of ctDNA as a powerful prognostic biomarker for GI cancers, along with its impact on risk stratification and the detection of recurrence. They highlight key studies in ctDNA that were featured at the 2024 ASCO GI Cancers Symposium, including COBRA, GALAXY, and BESPOKE in CRC, as well as the promise of ctDNA testing in the preoperative detection of iCCA. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Shaalan Beg, your guest host for the ASCO Daily News Podcast today. I am an adjunct associate professor at UT Southwestern's Harold Simmons Comprehensive Cancer Center in Dallas. On today's episode, we will be discussing the emergence of circulating tumor DNA (ctDNA) technology in GI cancers. I am delighted to be joined by Dr. Aparna Parikh, an assistant professor of medicine at Harvard University and the director for colorectal medical oncology at the Massachusetts General Hospital Cancer Center, where she also serves as the medical director of the Young Adult Colorectal Cancer Center. Dr. Parikh will share her insights on key research on this hot topic in GI oncology that was featured at the recent ASCO Gastrointestinal Cancers Symposium.  Our full disclosures are available in the transcripts of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Dr. Parikh, it's great to have you on the podcast today. Dr. Aparna Parikh: Thanks so much, Dr. Beg.  Dr. Shaalan Beg: In recent years, it has become evident that liquid biopsy and other emerging ctDNA technologies are changing how we treat GI cancers, and colorectal cancer (CRC) is in the forefront of this space. Before we dive into key studies, can you briefly highlight for our listeners how ctDNA is advancing the field and how it can influence the care that we deliver to our patients in the future? Dr. Aparna Parikh: Absolutely, ctDNA is certainly a hot topic. What we have learned over the years is that ctDNA has emerged across many solid tumor types as one of the most powerful, if not the most powerful, prognostic biomarker we have to date. ctDNA has improved risk stratification. We have learned a lot about the role in what is called minimal or molecular residual disease in patients with early-stage disease, and ctDNA being a biomarker of recurrence for those patients, with ctDNA, we have a better understanding of tumoral heterogeneity, both spatially and temporally, getting a better glimpse of what is happening in a given patient with multiple metastases, as well as genomic evolution of tumors over time. So certainly many, many roles and areas where ctDNA is emerging. Dr. Shaalan Beg: This was a hot topic at the 2024 ASCO GI Cancers Symposium, and we're going to take a deep dive into some of the abstracts that were presented. Let's start with the COBRA study, which is the NRG-GI005. That was Abstract 5 at the ASCO GI Cancers Symposium, and the GALAXY study, which was Abstract 6 at the symposium. So, the COBRA study reported results of ctDNA as a predictive biomarker in adjuvant chemotherapy for people with colon cancer. At a high level, it was a negative study, but there are some important lessons for us to learn. Similarly, in the GALAXY study, investigators from Japan presented an updated analysis on the correlation of ctDNA dynamics with outcomes in colorectal cancer with minimal residual disease. How do you synthesize all this information and help the listeners understand our current state for ctDNA applications in colorectal cancer? Dr. Aparna Parikh: Yeah. Let's take the COBRA study first. Let's talk a little bit about the design of COBRA. COBRA was intended to look at patients that were resected, stage 2 colorectal cancer patients, or colon cancer patients who were 2A. These are patients where the treating physician would, at the outset, decide that there was no adjuvant chemotherapy indicated. These are patients where