Real-world validation of the Khorana risk score in gastric cancer patients receiving immune checkpoint inhibitors.

363 Background: Thrombosis is a common cancer-related complication, particularly in gastric cancer. Studies show that immune checkpoint inhibitors (ICIs) increase the risk of venous thromboembolism (VTE) and arterial thrombosis. The Khorana risk score is widely used to assess thrombosis risk before starting chemotherapy. This study aimed to validate the Khorana score in gastric cancer patients receiving ICIs using a large global database. Methods: We used the TriNetX Global Collaborative Network, which contains de-identified data from over 120 million patients. We included patients diagnosed with gastric cancer who received ICIs between January 2014 and July 2023. The Khorana risk score was calculated based on lab values and BMI within two weeks before ICI initiation. Patients were divided into two cohorts: elevated risk (score 3-6) and intermediate risk (score 2). Cox-proportional hazard analyses were conducted over a one-year follow-up. The primary outcome was VTE (deep vein thrombosis [DVT] and pulmonary embolism [PE]). Secondary outcomes were arterial thrombosis, including myocardial infarction (AMI) and ischemic stroke, and all-cause mortality. Results: The study included 551 patients, with 362 in the intermediate risk and 189 in the elevated risk cohorts. The mean age was 64 in both cohorts, with the elevated group consisting of more males (76% vs. 63%) and a higher proportion of Black patients (11% vs. 6%). Pembrolizumab (49%) and nivolumab (47%) were the most used ICIs. Patients with elevated risk had a significantly higher risk of VTE (HR 1.74, 95% CI 1.18-2.58), DVT (HR 1.82, 95% CI 1.07-3.10), and PE (HR 1.74, 95% CI 1.07-2.84). However, no significant associations were found with arterial thrombosis (HR 1.28, 95% CI 0.74-2.20), including cerebral infarction (HR 1.05, 95% CI 0.51-2.16), or AMI (HR 1.46, 95% CI 0.70-3.05). The elevated risk cohort also had significantly higher mortality (HR 1.44, 95% CI 1.11-1.87). Conclusions: An elevated Khorana risk score is associated with a higher risk of VTE, but not arterial thrombosis, in gastric cancer patients treated with ICIs. Further studies are needed to determine how the Khorana score can be applied to predict ICI-related thrombosis and guide prophylactic anticoagulation. Outcomes Khorana risk score 3-6 Khorana risk score 2 Hazard ratio(95% CI) P-value(Log-rank) At risk patients Cases At risk patients Cases Venous thromboembolism 189 45 362 58 1.74 (1.18-2.58) 0.005 Deep vein thrombosis 189 25 362 30 1.82 (1.07-3.10) 0.025 Pulmonary embolism 189 29 362 36 1.74 (1.07-2.84) 0.025 Arterial thrombosis 189 21 362 34 1.28 (0.74-2.20) 0.375 Cerebral infarction 189 11 362 22 1.05 (0.51-2.16) 0.901 Acute myocardial infarction 189 12 362 17 1.46 (0.70-3.05) 0.317 All-cause mortality 189 93 362 145 1.44 (1.11-1.87) 0.006