Evaluation of the NorthStar ctDNA assay for monitoring gastrointestinal malignancies: A retrospective analysis.

Abstract

e15058 Background: Liquid biopsies offer a non-invasive alternative to traditional tissue biopsy for guiding therapy and response monitoring. However, current assays are limited by poor sensitivity and need a prior tissue sample. NorthStar Select and Response are tumor-naïve assays that utilize novel aneuploidy and methylation-based analytics to improve circulating tumor DNA (ctDNA) detection over competing methods. The short half-life of ctDNA is approximately 1-2 hours, making it valuable for real-time response monitoring. This study aims to provide descriptive analysis of Northstar and evaluate its potential for clinical utility in cancer monitoring and therapy selection. Methods: A single-institution, retrospective analysis was conducted on 99 patients with gastrointestinal cancers treated at UCI Medical Center. Blood samples collected between December 2019 and July 2025 were analyzed using the NorthStar platform, which included the Response assay’s methylation-based ctDNA quantification. Clinical and radiographic data were extracted to assess correlations between ctDNA dynamics, imaging findings, and treatment response. R was used for statistical analysis. Results: A total of 99 patients were included in the study, of whom 53 were male and 46 were female. 91 percent of individuals were in the 45-90 age range. 23 percent of patients identified as Hispanic, 74% as non-Hispanic, and 3% as unknown. 56% were White, 18% Asian, 13% mixed race, 2% Black or African American, and 11% other or unknown. The most common cancers were pancreatic (49%), colorectal (23%), unknown primary (10%), and cholangiocarcinoma (10%). At diagnosis, 48 patients had localized disease, while others had metastases to the liver (26), lung (18), peritoneum (9), lymph nodes (3), bone (3), brain (1), or other sites (6). 335 lines of therapy were recorded, including chemotherapy (165), targeted therapy (52), radiation (45), immunotherapy (26), clinical trial (40), and mixed therapies (7). 2235 tumor marker tests were performed: CEA (852), CA 19-9 (1303), CA 125 (36), and other (40). NorthStar ctDNA levels were available for 87 patients (mean 5,865; median 130; range 0–120,000). ctDNA became positive a mean of 153 days before radiographic recurrence. Initial ctDNA positivity rates were 76.2% for localized disease, 76.5% for lung metastases, and 74.1% for any metastatic disease. Conclusions: In this cohort of 99 patients with gastrointestinal cancers, the Northstar test demonstrated broad applicability across age groups, cancer types, and stages, including localized and metastatic disease. Initial ctDNA positivity was high across disease groups and metastatic status. The assays provided quantitative ctDNA measurements that may complement traditional markers and imaging, supporting their potential utility for real-time therapy monitoring and clinical decision-making.