Low Muscle Mass and Treatment Tolerance in Patients With Upper Gastrointestinal Cancer: A Systematic Review and Meta‐Analysis

Background: Upper gastrointestinal (GI) cancers carry notable mortality risks. While systemic therapies are vital for their management, they are often hindered by adverse events (AE), which can compromise their effectiveness. The presence of low skeletal muscle mass (LSMM) may be linked with the prevalence of AE and could potentially undermine treatment tolerance by impacting drug metabolism. The primary objective of this systematic review and meta‐analysis was to evaluate the association between LSMM and the risk of grades 3 and 4 AE and treatment discontinuation.

Methods: Studies investigating the association between skeletal muscle mass and AE or treatment tolerability in adult patients diagnosed with upper GI cancer scheduled to undergo systemic treatment were eligible. The primary outcomes were grades 3 and 4 AE and treatment discontinuations. Four electronic databases were systematically searched with no date restrictions on 10 October 2022. Data were analysed via random‐effects meta‐analyses, and the risk of bias was assessed using the risk of bias in non‐randomised studies—of exposure (ROBINS‐E) appraisal tool.

Results: We identified 50 eligible publications from 49 studies. Our meta‐analyses revealed evidence of a higher risk of grades 3 and 4 AE (RR 1.44, 95% CI 1.23–1.68, N = 13) and treatment discontinuation (RR 2.39, 95% CI 1.87–3.07, N = 11) in LSMM versus non‐LSMM. Secondary analyses revealed an increased risk of fatigue, febrile neutropenia, intestinal pneumonia, stomatitis and thrombocytopenia in LSMM. However, 92% of studies assessing grades 3 and 4 AE and 73% of studies examining treatment discontinuation had a very high risk of bias.

Conclusions: LSMM in patients with upper GI cancer is associated with a higher risk of grades 3 and 4 AE and the discontinuation of systemic cancer treatment. The high risk of bias should be considered in the interpretation of these findings. Further evaluation of the association between LSMM and treatment tolerability in confirmatory, prospective studies is needed.