Citations

830 Background: Immune checkpoint inhibitors (ICIs) are standard therapy for MSI-H GI cancers. Lynch syndrome, caused by germline mutations in mismatch repair (MMR) genes, leads to MSI-H tumors and robust ICI responses, but its effect on irAEs remains poorly defined. Clarifying this risk may inform treatment selection and toxicity monitoring. Methods: We retrospectively reviewed MSI-H or MMR-deficient (dMMR) GI cancer patients (pts) treated with ICIs across Mayo Clinic (AZ, MN, FL) from January 2017 to June 2025. Eligible pts were identified using Mayo Data Explorer. Demographics, treatment, and irAEs (graded per CTCAE v5.0) were collected. Lynch status was determined by germline testing when available. Logistic regression estimated odds ratios (ORs) for any grade and grade ≥3 irAEs, adjusting for age, cancer type, prior chemotherapy, and treatment regimen. Results: A total of 209 pts with dMMR/MSI-H GI cancer were included: 61 with Lynch syndrome and 148 without. Lynch pts were younger (median 58 vs 76 years, p < 0.001) and more likely to have received prior chemotherapy (62% vs 43%, p = 0.009). Colorectal cancer was the predominant cancer type (74%), but Lynch pts had proportionally more non-colorectal GI cancers (15% vs 2.7%, p = 0.007). Overall, 29% of pts experienced an irAE, with rates significantly higher in Lynch vs non-Lynch pts (43% vs 24%, p = 0.005). The most frequent irAEs were gastrointestinal, endocrine, and dermatologic, followed by hepatic and pulmonary events. Grade ≥3 irAEs occurred in 16% overall, with no significant difference between groups (p = 0.124). In adjusted models, Lynch syndrome was independently associated with a higher risk of any grade irAE (OR 2.14, 95% CI 1.09 - 4.19, p = 0.026), while risk of severe irAEs was not increased (OR 1.55, 95% CI 0.64 - 3.59, p = 0.316). Lynch syndrome pts were more likely to have combination therapy (17% vs 6.8%, p = 0.029). However, there were no differences observed in any grade irAE between monotherapy and combination immunotherapy (OR 1.36, 95% CI 0.49 - 3.54, p = 0.535). Conclusions: Lynch syndrome is associated with a higher prevalence of any-grade irAEs among dMMR/MSI-H GI cancer pts treated with ICIs, though severe events were not increased. Incorporating Lynch status into immunotherapy planning may improve risk stratification and guide regimen selection.

83 Background: Colon cancer is among the leading causes of cancer-related morbidity and mortality globally, with an increasing incidence observed in younger populations. Lifestyle and metabolic risk factors seem to play an important role in this rising incidence. Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity. Emerging evidence suggests that these agents may have potential anti-tumor activity as GLP-1 signaling may influence pathways involved in cell proliferation and inflammation. Our study aims to evaluate the impact of GLP-1 receptor agonists on outcomes among patients with colon cancer with comorbid obesity, exploring potential interactions between metabolic modulation and disease behavior. Methods: A retrospective cohort study was conducted using the US Collaborative Network TriNetX, covering January 2000 to December 2023, encompassing data from 105 global healthcare organizations. Adult patients aged 18 and above with colon cancer and comorbid obesity were identified and then stratified into two groups based on treatment with GLP-1 agonists or not. The two groups were then propensity-matched based on age, sex, race, and common comorbidities. We followed these patients for 5 years to assess outcomes, including overall mortality, myocardial infarction, sepsis, acute pancreatitis, need for mechanical ventilation and hemodialysis. Results: We identified 1986 patients with colon cancer and obesity who received GLP-1 receptor agonists, and 16384 patients with colon cancer and obesity who did not receive GLP-1 therapy. The average age was 68.8 years in the first cohort and 74.3 years in the second cohort. After propensity matching, each cohort consisted of 1983 patients with similar baseline characteristics and ethnicity distribution. Our analysis found that over 5 years, patients with colon cancer and obesity who received GLP-1 receptor agonists had a significantly lower risk of overall mortality (Hazard Ratio (HR): 0.461, 95% CI: 0.401 to 0.532, p-value < 0.001), myocardial infarction (HR: 0.827, 95% CI: 0.668 to 0.993, p-value =0.005), sepsis (Risk Difference: -3.48%, 95% CI: -4.774 to -2.185, p-value < 0.001), and need for mechanical ventilation (HR: 0.486, 95% CI: 0.321 to 0.739, p-value = 0.037). There was no statistically significant difference in the risk of acute pancreatitis and need for hemodialysis between the two subgroups. Conclusions: Our study revealed that patients with colon cancer and obesity who received GLP-1 receptor agonists had a significantly lower risk of mortality, myocardial infarction, sepsis, and need for mechanical ventilation. Further longitudinal cohort studies are imperative to better understand these associations and guide evidence-based clinical practice in this population.

817 Background: Universal germline sequencing is increasingly utilized in practice, but existing evidence and guidelines are based on studies in predominantly white populations. This study aims to compare the prevalence of genetic alterations in white vs underrepresented minority (URM) populations and assess incremental findings discovered with universal testing beyond current guidelines. Methods: This prospective, multicenter study analyzed genetic alterations in white and URM cohorts with primary GI malignancies receiving care at Mayo Clinic cancer centers between April 2018 and April 2025. Patients underwent germline sequencing using a next-generation sequencing (NGS) platform targeting over 80 genes. We compared the distribution of results between white and URM populations. Concordance with NCCN testing guidelines and incremental findings were assessed. Results: A total of 1128 patients were studied, of which 758 were white and 370 were URM, (47.6% Hispanic, 22.7% Black, 13.8% Asian, 10.5% American Indian, 0.8% Pacific Islander, and 6.8% other). Pathogenic variants (PGV) were more common in the white population (16.1% vs 9.2% P < 0.001). Variants of uncertain significance (VUS) were more common in the URM population (53.2 vs 43.5%, P<0.001). A total of 156 patients were found to have a PGV. PGVs outside primary cancer genes were more common in white patients (57.4% vs. 32.4%; p=0.0241). Incremental findings from universal testing were higher in white patients (66.4% vs 35.3%; p=0.0011). Conclusions: This study reveals a significant difference in the prevalence of PGV and VUS between white and URM patients with primary GI malignancies. The higher rate of PGVs in white patients and VUS in URM patients highlights potential inequities in both detection and interpretation of genetic results. These findings emphasize the need for broader representation in genetic databases to ensure equitable access to precision oncology. Screening guidelines met by patients with PGV. White (N=122) URM (N=34) Total (N=156) p value Did they meet NCCN testing guidelines for their primary cancer? 0.0991 Yes 87 (71.3%) 29 (85.3%) 116 (74.4%) No 35 (28.7%) 5 (14.7%) 40 (25.6%) Was the PGV outside of the primary genes recommended for their primary cancer? 0.0241 Yes 70 (57.4%) 11 (32.4%) 81 (51.9%) No 47 (38.5%) 22 (64.7%) 69 (44.2%) Incremental Finding 0.0011 Yes 81 (66.4%) 12 (35.3%) 93 (59.6%) No 41 (33.6%) 22 (64.7%) 63 (40.4%)

813 Background: Epidemiological data on gastrointestinal (GI) cancers in conflict-affected regions such as Syria are severely limited. Our study aims to fill in significant gaps in data by evaluating the demographics of Syrian patients diagnosed with new GI malignancies over a three-year period. Methods: This is a retrospective epidemiological study conducted at Al-Bairouni University Hospital – Syria’s national cancer center serving 60-70% of the country’s cancer patients. We included all patients diagnosed with GI malignancies (esophagogastric [EG], hepatocellular [HCC], biliary tract [BTC], pancreatic [PC], colorectal [CRC] cancers, and others) between Jan 2022 - Dec 2024. Data extracted from hospital records included sex, age at diagnosis, cancer stage, smoking status, and governorate of residence. Patients were grouped by disease group and year to assess annual trends. Institutional ethical approval was obtained to perform the study. Results: A total of 3,493 patients were diagnosed with GI cancers during the study period: 1,220 in 2022, 905 in 2023, and 1,368 in 2024 (Table 1). Across all years, a consistent male predominance was observed (60.1%). The average age at diagnosis was 59 years, 37.8% of patients were smokers, and 48.3% of all cases had advanced/metastatic disease at diagnosis. CRC (1,779) and EG (830) were the most common GI cancers. The highest patient loads originated from Damascus (17.6%) and Rural Damascus (17.5%), followed by central governorates such as Homs (9.7%) and Hama (9.3%). Notably, patients from more distant and underserved governorates such as Deir ez-Zor (7.0%), Aleppo (6.58%), and Al-Hasakeh (6.79%) accounted for a significant proportion of the GI cancers presenting to our center. Conclusions: To our knowledge, this study provides the first comprehensive multi-year dataset of GI cancers in Syria, with representation from all 14 governorates in the country. More than a third of our cohort were smokers and nearly half were diagnosed with advanced disease, demonstrating a need for public heath efforts to tackle tobacco use and improve screening & early detection. This dataset offers a foundation for future public health planning and research efforts in the region. Demographics of GI cancers diagnosed 2022-2024. Diagnosis 2022 Cases 2023 Cases 2024 Cases Total Cases Average Age Male Sex (%) Smokers (%) Advanced/Metastatic at diagnosis EG 311 217 302 830 56.1 519 (62.5%) 379 (45.7%) 370 (44.6%) HCC 88 46 61 195 59.2 134 (68.7%) 82 (42.1%) 116 (59.5%) BTC 34 43 54 131 58.4 69(52.7%) 40 (30.5%) 79 (60.3%) PC 118 122 160 400 58.4 249 (62.3%) 180 (45%) 247 (61.8%) CRC 620 444 715 1779 57.6 1008 (56.7%) 582 (32.7%) 805 (45.2%) Others (anal, small intestine, unknown primary) 49 33 76 158 55.5 75 (47.5%) 59 (37.3%) 69 (43.7%)

809 Background: Barriers to necessary care can pose a significant burden on patients with cancer, even more so in places of conflict. Following a devastating 14-year war in Syria, there is limited data published on access to cancer care and the impact that barriers to management have on our patients. We surveyed patients presenting for cancer care to better understand the challenges they faced. Methods: This cross-sectional study included adult patients with a confirmed gastrointestinal (GI) cancer diagnosis presenting to Al-Bairouni University Hospital for care. Data was collected through face-to-face interviews using a structured questionnaire adapted for the Syrian context. The survey covered six key areas: Demographic & Clinical, Healthcare System Barriers, Financial Barriers, Geographic & Security Barriers, Reasons for Diagnostic Delays, and Psychosocial Impact. Multivariate analysis via logistic regression was conducted to determine which responses were associated with a higher odds ratio (OR) of having a late-stage (III/IV) cancer diagnosis. Results: A total of 122 patients diagnosed with a GI cancer were enrolled. The mean age was 57.4 years (±11.2 SD), with a male predominance (68%, n=83). Advanced diagnostics (CT/MRI/biopsy) and radiation therapy were inaccessible for 55% (n =67) and 61% (n =74) of patients, respectively. Systemic therapy drugs were "rarely" or "never" available for 35% (n=43) of patients, and 12% (n=15) reported waiting over three months for an appointment. The costs of medications "greatly" or "very greatly" impacted 88% (n=107) of patients. Over two-thirds of patients reported that essential pain control medications (e.g., morphine) were "rarely" or "never" available (68%, n=83). Nearly two-thirds (65%, n =79) reported that security concerns "greatly" or "somewhat" affected their ability to access treatment. An overwhelming 87% (n=106) of patients reported a negative psychological impact from their treatment course. Patient responses associated with a higher OR of late-stage cancer diagnosis are present in the table. Conclusions: Patients in Syria with GI cancers face profound systemic, financial, geographic, and psychosocial challenges throughout their care journey. More than half were diagnosed at advanced stages, with diagnostic delays strongly linked to prolonged waiting times and financial strain. Financial toxicity was highly evident, resulting in treatment compromise and asset liquidation. This data should serve as a reference for future public health and humanitarian efforts in the region. Factors associated with late-stage (III/IV) diagnosis of GI malignancies (multivariate logistic regression). Variable Adjusted Odds Ratio (aOR) 95% Confidence Interval p-value Waiting Time First Oncology appointment >1 month 3.10 1.45 - 6.62 0.003 * Unemployed due to cancer 2.85 1.20 - 6.78 0.018 * Sold Assets to Finance Care 2.40 1.10 - 5.25 0.028 * *Statistically significant at p < 0.05.

800 Background: Primary squamous cell carcinoma (SCC) of the small intestine is exceedingly rare and associated with poor prognosis. Literature is currently limited to a few case reports, and, to our knowledge, this is the first population-based analysis of patients with small intestine SCC. This study aimed to identify patient demographics and predictors of survival outcomes. Methods: Patients with histologically confirmed primary SCC of the small intestine diagnosed between 2000 and 2022 were identified from the SEER database; autopsy-only cases were excluded. Patient demographics, tumor site, stage (SEER summary stage), and initial treatments were summarized. Overall survival (OS) was defined from diagnosis to death, with one-year OS estimated by Kaplan–Meier methods. Multivariate Cox proportional hazards models evaluated associations between patient variables (age, sex, race, residence, year of diagnosis, surgery, and chemotherapy) and mortality. All statistical analyses were performed using R version 4.4.2. Results: A total of 89 patients diagnosed with primary small intestine SCC were identified. The median age at diagnosis was 68 years; 43 % were female, and 67 % were non-Hispanic White. Most patients (82 %) resided in urban counties. Tumor site was mostly the duodenum (37 %), followed by ileum (16 %) and jejunum (10 %); 33 % were not otherwise specified. Among patients with a recorded stage, 45 % had localized disease, 38 % regional disease, and 17 % distant metastases. Initial treatment comprised surgery in 60 % of patients, chemotherapy in 25 %, and radiation in 10%. The median OS was approximately six months, and the one-year OS was 36.7 % (95 % CI 27.9–48.3). Women had a higher one-year OS (42 %) than men (33 %), although this difference was not statistically significant. In multivariable analysis, surgical resection was associated with a markedly lower hazard of death (HR = 0.43, 95 % CI 0.25–0.74). Chemotherapy was associated with an insignificantly improved survival (HR 0.54, 95 % CI 0.27–1.09). Additionally, rural residence (HR ≈ 2.9) and older age (HR ≈ 1.03) were independently associated with worse survival (p<0.05). Conclusions: This population-based study highlights the rarity and aggressiveness of primary small bowel SCC, with a median OS of six months. Surgical resection was strongly associated with improved survival (adjusted HR ≈ 0.43), reinforcing its role as the cornerstone of management. Chemotherapy showed a nonsignificant survival benefit, highlighting the need for prospective studies. The association of rural residence with higher mortality suggests disparities in access to care and underscores the need for strategies to improve early detection and referral. Overall, these findings support a multimodal approach centered on surgery and warrant further studies to elucidate pathogenesis and optimize systemic therapy.

776 Background: Surgery is the only potentially curative option for PC. However, only a minority of patients (pts) undergo resection with current perioperative (periop)-chemotherapy (CT). In the absence of phase III trials, selection between mFOLFIRINOX and gemcitabine/nab-paclitaxel (gem-nab) is based on limited evidence. We assessed whether NGS–based tumor profiling can guide tailoring of CT. Methods: pts with resected PC (resectable, borderline resectable, and downstaged locally advanced) that underwent Tempus xT, xF (DNA), and/or xR (RNA) testing were selected (89% tissue, 11% blood). Most samples (73%) were collected post-CT. Samples were stratified by KRAS status into KRAS -mutated ( KRAS mut) and KRAS wild-type ( KRAS wt). PD-L1 IHC was reported as tumor proportion score (TPS). Primary endpoint was median overall survival (mOS) defined from CT initiation to death with censoring of pts alive at the last follow-up or at a study cutoff of 5 years. Secondary endpoint was molecular profiling by KRAS status. Pearson chi-square and Wilcoxon rank-sum tests were used for descriptive comparisons; univariate Cox regression and log-rank tests (p<0.05) for survival. Results: We included 1,325 pts (median age 66 years [IQR 59–72]) with resected PC [stage II (15%), stage III (12%) and stage I (10%), unknown (62%)]. 95% had adenocarcinoma. Pts received neoadjuvant (50%), neoadjuvant plus adjuvant (26%), neoadjuvant with indeterminate adjuvant allocation (13%) or adjuvant CT (11%). First-line periop-CT was mFOLFIRINOX in 73% and gem-nab in 27% (median duration 4.3 months (mo) [range, 2.6–6.7]). KRAS mutations were present in 75% (G12X 91%: G12D 44%, G12V 34%, G12R 21%, G12C <1%). mOS was 26.7 mo (95%CI, 22.4-35.7) in the total cohort; KRAS mut pts showed a clinically meaningful worse mOS compared to KRAS wt [24.1 vs 35.7 mo; HR 1.61 (95%CI, 0.98 - 2.63); p=0.06]. In the KRAS G12D pts, mFOLFIRINOX showed a trend towards longer mOS compared to gem-nab [17.79 vs 14.53 mo; HR 0.75, (95% CI, 0.56 - 1); p=0.050]; no significant differences were observed in other KRAS subgroups. Compared to KRAS wt, KRAS mut pts were enriched for TP53 (76% vs 22%; p<0.001), SMAD4 (28% vs 5.8%; p<0.001), CDKN2A (33% vs 8.5%; p<0.001), MTAP deletions (7.7% vs 1.2%; p<0.001), and chromatin-regulator alterations ( ARID1A 7.8% vs 1.2%; p<0.001; KMT2C 2.5% vs 0.6%; p=0.034). KRAS wt pts were enriched for BRAF V600E (1.5% vs 0%; p<0.001). PD-L1 TPS ≥1% was more frequent in KRAS mut compared to KRAS wt (11.0% vs 8.1%; p=0.033). Conclusions: KRAS status does not predict benefit from mFOLFIRINOX vs gem-nab in resected PC. Interestingly, resected PC showed a higher prevalence of KRAS wt compared to the metastatic setting. KRAS status is associated with distinct profiles of potentially targetable co-alterations. These findings may suggest the integration of genomic profiling in clinical trials to develop biomarker-driven tailored strategies in the early stage.

761 Background: Glycogen Synthase Kinase-3β (GSK-3β) is a known therapeutic target in cancer including pancreatic adenocarcinoma (PDAC). The combination of elraglusib (9-ING-41), a novel GSK-3 inhibitor, and gemcitabine/nab-paclitaxel (GnP) is being evaluated as first-line therapy for patients with metastatic PDAC (mPDAC). We previously reported topline results indicating that the 1801 Part 3B phase 2 trial (NCT03678883) met its primary endpoint, showing a clinically meaningful survival benefit in patients treated with elraglusib/GnP compared to GnP alone. Here, we examined whether gene mutations correlated with clinical outcomes in mPDAC patients enrolled in this randomized phase 2 trial. Methods: For mutational analysis, archival tumor and/or plasma samples were obtained from 53 (GnP group) and 117 (elraglusib/GnP group) patients with previously untreated mPDAC. Cell-free DNA and/or tumor-extracted DNA were analyzed using the next generation sequencing. The comparison of the response rates was performed with the use of Chi-square tests. Kaplan-Meier survival curves were compared by log-rank (Mantel-Cox) tests. Results: Mutational analysis identified frequently mutated genes (detectable in ≥25% of patients): KRAS (141/170, 83%), TP53 (121/170, 71%), and CDKN2A (56/170, 33%). Mutations in KRAS, TP53, or CDKN2A genes did not correlate with objective response rate. Based on 81% of the recorded death events in the elraglusib/GnP group and 91% in the GnP group (topline data April, 2025), KRAS and TP53 gene mutations were associated with worse overall survival (OS) in patients treated with elraglusib/GnP (p<0.05) but not in GnP-treated patients. The rate of triple (KRAS+TP53+CDKN2A) mutations was significantly higher in the patients with OS<2 months as compared to the patients with OS>2 months in the elraglusib/GnP group (p<0.05) but not in the GnP group. Conclusions: Our preliminary results identified KRAS and TP53 gene mutations as potential predictive biomarkers of clinical outcome in elraglusib/GnP-treated mPDAC patients. Updated OS data and mutational analysis will be included in the final presentation. Clinical trial information: NCT03678883 .

741 Background: IP strategies directly target the peritoneal compartment in PDAC, where systemic chemotherapy alone demonstrates poor efficacy. Approaches include HIPEC, normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX) given with systemic therapy, and PIPAC. This systematic review synthesizes evidence on feasibility, perioperative safety, and clinical outcomes of IP therapy in PDAC. Methods: We conducted a systematic search in PubMed, Embase, Scopus, and Cochrane databases for studies published through August 2025. Eligible studies included prospective or retrospective studies evaluating HIPEC, NIPEC/IP-PTX, or PIPAC with extractable safety or oncologic outcomes. Outcomes included feasibility, 30-day mortality, perioperative complications, locoregional recurrence (LRR) in the adjuvant setting, overall survival (OS) from peritoneal metastasis (PM) diagnosis or first IP therapy, conversion-to-resection, and histologic/radiologic response. Results: Sixteen studies met criteria, including 7 on HIPEC, 5 on NIPEC/IP-PTX, and 4 on PIPAC. In the adjuvant setting, 2 HIPEC studies demonstrated high feasibility (>85%), 0–5% 30-day mortality, and complication rates comparable to pancreatectomy. A randomized trial reported significantly lower LRR with adjuvant gemcitabine HIPEC. Median OS in treated arms was ~17–18 months, with 1-year OS ~63%. In the cytoreductive surgery (CRS) plus HIPEC setting for isolated peritoneal metastases, patients achieved CC-0/1 cytoreduction in most cases, with median OS ~24–41 months and 1-, 2-, and 3-year OS ranging 60–91%, 33–66%, and 39–59%, respectively. Thirty-day mortality was 0–4.3%, and major morbidity 20–43%. For NIPEC/IP-PTX, multicenter and single-institution cohorts consistently reported median OS ~14–16 months, 1-year OS ~60%, and conversion-to-resection rates of 17–24%. Ascites control and feasibility were reproducible, and device-related adverse events were generally manageable. PIPAC programs established oxaliplatin at 120 mg/m² as the recommended dose, with ~50–60% histologic regression by PRGS and disease stabilization in 50–60% after 1–2 cycles. Median OS in PDAC subsets was ~9–13 months, with low major toxicity, though early discontinuation was frequent in progressive disease. Conclusions: Intraperitoneal therapies for PDAC are feasible and show promising biologic and clinical signals. Adjuvant HIPEC reduces locoregional recurrence without excess mortality; CRS plus HIPEC can achieve multi-year survival in selected patients with isolated PM metastases; NIPEC/IP-PTX offers reproducible survival and conversion-to-resection; and PIPAC provides histologic regression with acceptable safety.

733 Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have advanced the treatment of type 2 diabetes mellitus (T2DM) yet their association with cancer risk remains subject of ongoing research. While case reports and pharmacovigilance data have linked GLP-1RA’s to pancreatitis, large randomized trials and observational studies have not consistently shown an increased risk of pancreatic cancer. Chronic pancreatitis (CP) is a well-established risk factor for pancreatic cancer, yet the impact of GLP-1 RA therapy in this high-risk population is unknown. In this study, we aim to evaluate the association between GLP-1 RA use and pancreatic cancer incidence among patients with CP, and among those with CP and T2DM. Methods: We performed a retrospective cohort study using ICD-10 codes within TriNetX, a healthcare database of over 150 million patients in the United States. In the first analysis, adult patients with pre-existing CP were identified, and the 5-year incidence of pancreatic cancer between GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, and lixisenatide) users and non-users was compared from 2015-2025. In the subsequent analysis, we restricted the cohort to adults with CP and T2DM and repeated the comparison. Patients with prior diagnosis of pancreatic cancer were excluded from both analyses. All cohorts were propensity score matched (PSM) on age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, and pancreatic cysts. Results: We identified 95,391 with CP, including 3,139 GLP-1 RA users and 92,252 non-users. After PSM, GLP-1 RA use was associated with a lower incidence of pancreatic cancer (0.6% vs. 1.5%, OR 0.39 [0.22, 0.67]). Similarly, amongst patients with CP and T2DM, GLP-1 RA use was associated with a lower incidence of pancreatic cancer (0.7% vs. 1.6%, OR 0.44 [0.25, 0.75]). Conclusions: GLP-1 RA use was associated with a significantly reduced incidence of pancreatic cancer in all patients with CP and in those with CP and T2DM. Given the elevated cancer risk in CP, these findings suggest a potential protective effect of GLP-1RA use in this high risk population. Prospective studies will be important to further analyze and confirm this potential benefit.