TIP3. A prospective feasibility study using preoperative ctDNA to tailor neoadjuvant chemotherapy for patients with colorectal or appendiceal adenocarcinoma

Friday, March 6, 2026

3:55 PM - 3:59 PM MST

Location: Immuno-Oncology HUB Zone

Co-Author(s)

Taylor Neilson, MD

Surgical Oncology T32 Research Fellow
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX, USA.
Houston, Texas, United States
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Y. Nancy You, MD, MHSc

Professor
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Brian K. Bednarski, MD (he/him/his)

Associate Professor
MD Anderson Cancer Center
Houston, Texas, United States
Ramy Behman, MD, PhD

Assistant Professor
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Tsuyoshi Konishi, MD, PhD

Associate Professor
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Craig A. Messick, MD

Associate Professor
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Beth A. Helmink, MD, PhD (she/her/hers)

Assistant Professor
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Yun Song, MD (she/her/hers)

Assistant Professor
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center
Houston, Texas, United States
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Keith F. Fournier, MD

Associate Professor
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center
Houston, Texas, United States
J. Joshua Smith, MD, PhD

Professor and Chair
Department of Colon & Rectal Surgery, University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Paula Marincola Marincola Smith, MD, PhD

Assistant Professor of Surgery
Department of Colon & Rectal Surgery, University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Michael G. White, MD, MS

Assistant Professor, Director of Research
Department of Colon and Rectal Surgery, University of Texas MD Anderson Cancer Center
Houston, Texas, United States

Primary Presenter(s)

Ryan B. Morgan, MD

Fellow
MD Anderson Cancer Center
Houston, Texas, United States

Background: Treatment paradigms for patients with p</span>eritoneal metastases (PM) secondary to either colorectal cancer (CRC) or appendiceal adenocarcinoma (AA) are heterogeneous. Patients with resectable disease have improved survival following cytoreductive surgery (CRS) as part of multimodal care with the addition of peri-operative systemic chemotherapy being beneficial for patients with moderately or poorly differentiated histology. The ideal sequencing of treatment, however, remains unclear, and there are no well-established criteria for duration of neoadjuvant chemotherapy. Standard chemotherapy regimens for these patients can be poorly tolerated with cumulative toxicity affecting peri-operative outcomes. Circulating tumor DNA (ctDNA) has recently been studied as a decision tool for adjuvant treatment; however, it remains an unstudied marker for pre-operative risk-stratification. Given low ctDNA shedding with peritoneal metastases, preoperative ctDNA positivity has been previously noted to correlate with shorter disease-free survival and a higher rate of visceral metastases. While conversion to negative ctDNA during adjuvant treatment for CRC confers a similar survival benefit as compared to being seronegative immediately after surgery, the significance of a similar conversion prior to CRS to guide neoadjuvant treatment is unexplored.

Methods: This single-arm trial (NCT05947838) includes patients who are ≥18 years old with histologically confirmed CRC or moderately/poorly differentiated AA with resectable peritoneal disease. Patients receive 2-3 months of standard of care neoadjuvant chemotherapy, after which those with stable or improving disease on cross-sectional imaging have ctDNA levels drawn. Patients with negative ctDNA undergo laparoscopy followed by CRS +/- Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Those with persistently positive ctDNA receive an additional 2-3 months of chemotherapy prior to undergoing laparoscopy and CRS +/- HIPEC, with an option to change chemotherapy agents per standard of care recommendations. The primary endpoint is median recurrence-free survival (RFS) from the time of surgery, with secondary endpoints including 1- and 2- year RFS, 2-year overall survival, best overall response, patterns of recurrence, and rates of ctDNA conversion to negative. Eleven patients are currently enrolled with a target accrual of 48 patients over the coming 10-month period.

Learning Objectives:

Review current neoadjuvant treatment strategies for colorectal or appendiceal adenocarcinoma with peritoneal metastases.
Discuss the potential role for ctDNA in risk-stratifying patients with peritoneal carcinomatosis secondary to colorectal or appendiceal adenocarcinoma.