The Role of Body Composition on Drug Tolerance in Cancer Therapy: A Structured Narrative Review.

purpose of reviewThe aim of the present review is to analyse the current knowledge on how body composition parameters, principally low muscle mass (frequently reported as "sarcopenia") and myosteatosis (low muscle quality), relate to drug tolerance and the occurrence of adverse events during cancer therapy across different malignancies. RECENT

findingsBecause dosing based on weight or body surface area does not capture body composition, its potential limitations have increasingly been questioned. The available research spans a highly heterogeneous set of studies with inconsistent results. In non-small-cell lung cancer treated with platinum-based chemotherapy, low muscle mass has been associated with a nearly 2.5-fold increase in the risk of severe haematological toxicity, and with immunotherapy it has been reported as an independent predictor of severe immune-related toxicities with agents such as nivolumab. In ovarian cancer, low skeletal muscle radiodensity and low subcutaneous adipose tissue index independently predicted severe adverse events and treatment modifications. However, other studies-for example in pancreatic and thyroid cancer-found no significant association between baseline low muscle mass and short-term dose modifications or adverse outcomes. Studies differed markedly not only in the body-composition parameters measured and the definition of abnormal values, but also in how treatment tolerance was evaluated, which limits comparability across studies. The current literature suggests a biologically plausible but unconfirmed link between reduced skeletal muscle and treatment-related toxicity, potentially mediated by a lower distribution volume of hydrophilic agents such as platinum compounds and monoclonal antibodies, with a consequent rise in peak plasma concentrations. Nevertheless, the evidence is too heterogeneous and insufficiently standardized to draw robust conclusions and should be regarded as hypothesis-generating. Before body-composition assessment can be recommended for treatment planning or dose individualization in routine practice, the field requires standardized and validated assessment methods, harmonized diagnostic criteria, systematic adjustment for confounders, and adequately powered prospective studies.