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Thompson, Joshua and McGovern, Josh and Roxburgh, Campbell and Edwards, Joanne and Dolan, Ross D. and McMillan, Donald C. (2024) The relationship between LDH and GLIM criteria for cancer cachexia: systematic review and meta-analysis. Critical Reviews in Oncology/Hematology, 199: 104378. ISSN 1040-8428

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Abstract

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=2,165) on LDH and weight loss, 17 studies (n=7,540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 97 studies (n=37,185) 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, 1.60 – 2.16; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 – 1.99; p=0.0002) and had a similar OS (HR 2.01, 1.73 – 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 1.71, 1.60 - 1.82; p<0.00001) as elevated NLR (HR 1.57, 1.44 – 1.71; p<0.00001) or CRP (HR 1.53, 1.41 – 1.65; 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.

People

Thompson, Joshua

Author

Publications

Dolan, Ross D. and Pennel, Kathryn and Thompson, Joshua and McKenzie, Molly and Alexander, Peter and Richards, Colin and Black, Douglas and Abbass, Tanvir and Maka, Noori and McGovern, Josh and Roseweir, Antonia and McSorley, Stephen T. and Horgan, Paul G. and Roxburgh, Campbell and McMillan, Donald C. and Edwards, Joanne (2025) The relationship between tumour necrosis, systemic inflammation, body composition and survival in patients with colon cancer. BJC Reports, 3 (1): 7. ISSN 2731-9377

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McGovern, Josh

Author

Publications

Thompson, Joshua J. and MacLeod, Nicholas and Will, Sarah and O'Rourke, Fraser and McGovern, Josh and Roxburgh, Campbell and Edwards, Joanne and Dolan, Ross D. and McMillan, Donald C. (2025) The prognostic value of a laboratory cachexia score (LCAS) defined by LDH, CRP and albumin in patients with advanced lung cancer. BMC Cancer, 25: 543. ISSN 1471-2407

Golder, Allan M. and Ferguson, Michael and McMillan, Paul and Mansouri, David and Horgan, Paul G. and Roxburgh, Campbell S. and Dolan, Ross D. and McGovern, Josh and McMillan, Donald (2024) CT-derived body composition and differential association with age, TNM stage and systemic inflammation in patients with colon cancer. Scientific Reports, 14: 15673. ISSN 2045-2322

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Roxburgh, Campbell S. D.

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Bradley, Nicholas A. and Walter, Amy and Sankey, Chiara and Wilson, Alasdair and Siddiqui, Tamim and Roxburgh, Campbell D. and McMillan, Donald C. and Guthrie, Graeme J.K. (2025) Longitudinal association between statins and changes in CT derived body composition in patients with abdominal aortic aneurysm. Journal of Cachexia, Sarcopenia and Muscle, 16 (2). ISSN 2190-5991

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Edwards, J.

Author

Publications

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X