External validation of the Khorana score for the prediction of venous thromboembolism in cancer patients: A systematic review and meta-analysis☆

Background: Venous thromboembolism is the leading cause of death in cancer patients, second only to tumor progression. The Khorana score is recommended by clinical guidelines for identifying ambulatory cancer patients at high risk of venous thromboembolism during chemotherapy. However, its predictive performance is debated among cancer patients. Objectives: To map the applicability of the Khorana score in cancer patients and to assess its predictive performance across various cancer types, providing guidance for clinicians and nurses to use it more appropriately. Design: Systematic review and meta-analysis. Methods: A comprehensive literature search of the electronic database was first conducted on August 30, 2023, and updated on May 20, 2024. Studies examining the Khorana score's predictive performance (including but not limited to the areas under the curve, C-index, and calibration plot) in cancer patients were included. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was applied to evaluate the methodological quality of the included studies. Data synthesis was achieved via random-effects meta-analysis using the R studio software. The subgroup analysis was performed according to the study design, clinical setting, cancer type, anti-cancer treatment stage, and country. Results: The review incorporated 67 studies, including 58 observational studies and nine randomized controlled trials. All included studies assessed the Khorana score's discrimination, with the C-index ranging from 0.40 to 0.84. The pooled C-index for randomized controlled trials was 0.61 (95% CI 0.51-0.70), while observational studies showed a pooled C-index of 0.59 (95% CI 0.57-0.60). Subgroup analyses revealed the pooled C-index for lung cancer, lymphoma, gastrointestinal cancer, and mixed cancer patients as 0.60 (95 % CI 0.53-0.67), 0.56 (95 % CI 0.51-0.61), 0.59 (95% CI 0.39-0.76), and 0.60 (95 % CI 0.58-0.61), respectively. Inpatient and outpatient settings had the pooled C-index of 0.60 (95% CI 0.58-0.63) and 0.58 (95% CI 0.55-0.61), respectively. Calibration was assessed in only four studies. All included studies were identified to have a high risk of bias according to PROBAST. Conclusion: The Khorana score has been widely validated in various types of cancer patients; however, it exhibited poor capability (pooled C-index< 0.7) in accurately discriminating VTE risk among most types of cancer patients either in inpatient or outpatient settings. The Khorana score should be used with caution, and highquality studies are needed to further validate its predictive performance. (c) 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.