Personalized tumor-informed circulating tumor DNA analysis in monitoring recurrence following resection of high-risk stage II-III gastrointestinal stromal tumor.

11534 Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Radical resection is the standard treatment of localized GIST, yet the 5-year recurrence rate for high-risk GIST is more than 50%. It remains unclear whether detecting post-surgery molecular residual disease (MRD) via circulating tumor DNA (ctDNA) can predict the recurrence of high-risk locally advanced GIST. Methods: Patients with high-risk stage II-III GIST who underwent R0 surgery and following adjuvant imatinib/avapritinib were enrolled prospectively. Surgical tissue samples were collected. Blood samples were drawn pre-surgically, and at 7 days, 1 month, and every 3–6 months post-surgically. Tumor-derived variants were identified by whole-exon sequencing of the surgical tissues. Up to 50 highly ranked variants with a variant allele frequency 3.0% were selected for the personalized panel design, which was subsequently used to assess MRD status. Results: A total of 36 patients with a median age of 65 years were included in the current analysis (data cutoff on January 16, 2024). Most tumors (17/36, 47%) were located at the stomach or gastroesophageal junction, and 94.4% of patients (34/36) did not receive neoadjuvant treatment. The mean maximum diameter of tumors was 7.87 ± 2.87 cm. At present, 36 tissue samples, 34 pre- and 161 post-surgical blood samples were collected and analyzed. Tissue sample-based sequencing identified variants in KIT and PDGFRA in 31 (86%) and 4 (11%) patients, respectively. 98.4% (1003/1019) of tumor variants included in personalized panels were patient-specific. ctDNA was detected in 64.7% (22/34) of pre-surgical plasma samples. The ctDNA-positive rate at baseline was associated with tumor mutation burden (p < 0.05), rather than tumor size (p = 0.6). Landmark analysis at 1 week post-surgery showed that 12.1% of patients were positive for ctDNA. Up to now, 4 patients were identified with tumor recurrence based on imaging results. Among these patients, 3 patients (3/4) exhibited ctDNA positivity preceding radiological recurrence. Notably, a 71-year-old patient was ctDNA-positive at 1 week post-surgery. Longitudinal analysis revealed that his ctDNA became negative after adjuvant treatment but turned positive at 9 months post-surgery, with a lead time of 2 months prior to his radiological recurrence. Additionally, a patient tested positive for ctDNA at 3 months post-surgery but had negative imaging results. Follow-up visits are ongoing for this patient. Conclusions: The present study suggests that personalized tumor-informed ctDNA has the potential to inform recurrence in high-risk stage II-III GIST patients. Clinical enrollment is still ongoing.