Liquid biopsies are the detection of molecular information in fluids from patients with cancer. In colorectal cancer (CRC), the most promising liquid biopsy strategy is the use of circulating tumor DNA (ctDNA) from plasma. In early-stage CRC, the potential for ctDNA to impact care stems from the detection of minimal residual disease (MRD) to guide adjuvant therapy after curative intent treatment and in identifying recurrences during surveillance. As for any new diagnostic test, ctDNA assays must overcome pre-analytical and analytical challenges before clinical implementation. We will discuss important logistical and assay considerations that clinicians and patients should understand when assessing ctDNA assays. We will also delve into important concepts to aid in interpreting ctDNA results and potential incidental findings that may arise. Sequencing errors, germline variants, and clonal hematopoiesis of indeterminate potential (CHIP) must be addressed to properly interpret results. CHIP is also an important consideration that impacts patient prognosis through association with cardiovascular and hematologic diseases. With this background in place, we next review the best available evidence for the use of ctDNA in early-stage colon cancer. Observational cohorts have established MRD after surgery as a significant prognostic factor for recurrence in stage II and III colon cancer. It also has the ability to anticipate clinical recurrence before standard investigations when used in surveillance. The first and only interventional randomized trial to date evaluating ctDNA is DYNAMIC. The study demonstrated the noninferiority of a MRD detection-guided approach in selecting patients with stage II colon cancer for adjuvant treatment. Notwithstanding the important results, there are still important questions to be answered before ctDNA enters prime time in the clinic. However, future appears bright and ongoing trials will help clarify how to best use this technology in early-stage colon cancer.

124 Background: Primary tumour location is predictive of anti-EGFR benefit and prognostic in metastatic colorectal cancer (mCRC). Transverse colon cancers are often categorized as right sided, but the optimal cut point is unclear. Canadian Cancer Trials Group (CCTG)/Australasian Gastro-Intestinal Trials Group ( AGITG) CO.17 compared Cetuximab (Cet) vs. best supportive care (BSC) in mCRC. CCTG/AGITG CO.20 studied the addition of Brivanib Alaninate to Cet in pre-treated KRAS wildtype (WT) mCRC. We investigated the predictive and prognostic features of transverse colon primary location in a pooled cohort from these trials. Methods: Data from patients with RAS WT mCRC from CO.17 and KRAS WT mCRC from CO.20 randomized to cetux were analyzed for treatment outcomes according to location - right, transverse and left. The cecum to transverse colon was considered right sided, while the splenic flexure to rectum was considered left sided. Results: 553 patients were included, 201 (36.3%) from CO.17 and 352 (63.7%) from CO.20. Primary site distribution was: 32 (5.8%) transverse, 101 (18.3%) right and 420 (75.9%) left. On multivariate analysis from 457 (82.6%) patients treated with Cet, left side was associated with superior OS (HR, 0.40; 95% CI, 0.24-0.68, p=0.0006) and PFS (HR, 0.48; 95% CI,0.29-0.79, p=0.004) compared to transverse colon. No significant difference was noted in OS (HR, 0.74; 95% CI, 0.41-1.31, p=0.30) and PFS (HR, 0.79; 95% CI, 0.46-1.36, p=0.40) between right side versus transverse colon. Sidedness was not associated with prognostic difference in OS or PFS in the 96 (17.4%) patients receiving BSC alone. Outcomes according to primary site and treatment are shown. Conclusions: Transverse mCRC has comparable prognostic and predictive features to right sided mCRC. In keeping with previous studies, left side was predictive of greater Cet benefit and presented better overall prognosis when single agent Cet was used after 5-FU, oxaliplatin and irinotecan. [Table: see text]

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4022 Background: Somatostatin receptor imaging (SRI) is a standard of care for patients with GEPNETs. The additional value of concurrent 18F-FDG PET/CT (FDG PET) remains unclear. We reviewed a prospective functional imaging study to determine the utility of FDG PET in GEPNENs. Methods: PETNET is a prospective study in British Columbia, Canada, which provides all 68Ga-DOTA-TOC (DOTA PET) imaging in the province. Every patient receives a DOTA PET scan and an FDG PET within 30 days. PETNET enrolls all patients with an indication for SRI. Scans are ordered per treating physician discretion at any point in the disease course. This abstract focuses on the WD-GEPNEN population. Only the first dual functional imaging scans were analyzed and FDG was interpreted qualitatively (positive/negative). Results: From 04/2017-01/2023, 375 patients with NEN were enrolled, 165 (44%) with metastatic GEPNENs. Baseline characteristics are described. Median time between scans was 4 days (IQR 1-11). The proportion of patients with positive FDG PET at baseline increased with WHO grade. For patients with well differentiated G1 to G3 GEPNENs (N=161), overall survival was significantly lower with a positive FDG PET (HR: 4.22; 95%CI 1.61-11.02 p=0.001). FDG remained prognostic when G3 tumors were excluded (N=148) (HR 3.52; 95%CI 1.32-9.42 p= 0.007). When analyzing dual tracer PET imaging, patients with DOTA+/FDG- had reduced risk of dying in comparison with DOTA+/FDG+ (HR:0.26; 95%CI 0.09-0.67 p=0.01). After multivariate analysis, FDG positivity remained independently associated with reduced survival (HR 2.87; 95%CI 1.06-7.75 p=0.04) when controlling for grade of tumor and age. Conclusions: In this prospective cohort of metastatic GEPNENs, a positive FDG PET was significantly associated with reduced overall survival. These results provide additional evidence to support dual tracer functional imaging use in metastatic well differentiated GEPNEN’s. [Table: see text]