The relationship between LDH and GLIM criteria for cancer cachexia: Systematic review and meta-analysis

Introduction: Cancer cachexia is a clinical condition characterized by recognizable "sickness behaviors" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed. Methods: A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS). Results: A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n =2165) on LDH and weight loss, 17 studies (n =7540) on LDH and low BMI, 5 studies (n =758) on LDH and low muscle mass, 0 studies on LDH and food intake and 93 studies (n =32,190) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p =0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p <0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p <0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.57 - 2.07; p <0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p =0.0002) and had a similar OS (HR 2.00, 1.70 - 2.34; p <0.00001) to low BMI (HR 1.57, 1.29-2.90; p <0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p <0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p =0.01) and again, LDH conferred as poor an OS (HR 1.77, 1.64-1.90; p <0.00001) as elevated NLR (HR 1.61, 1.48 - 1.77; p <0.00001) or CRP (HR 1.55, 1.43 - 1.69; p <0.00001). Conclusion: Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria.