This structured narrative review evaluates current evidence on how body composition—mainly low skeletal muscle mass (often reported as sarcopenia) and poor muscle quality (myosteatosis)—relates to drug tolerance and the occurrence of adverse events during cancer therapy. The review addresses multiple malignancies and treatment types and focuses on whether body-composition measures predict increased treatment toxicity or modifications.
Body-composition assessment in oncology studies commonly quantifies skeletal muscle mass and radiodensity, adipose tissue compartments, and indices derived from cross-sectional imaging. The literature uses diverse parameters and variable diagnostic cutoffs, and studies often label low muscle mass as sarcopenia and low muscle radiodensity as indicative of myosteatosis or low muscle quality. The review emphasizes that conventional chemotherapy dosing based on weight or body surface area does not capture these compositional differences, which has motivated research into whether body composition better explains interindividual variability in toxicity.
The available studies are heterogeneous and yield inconsistent results across cancer types and therapies. Notable findings reported in the review include:
Non-small-cell lung cancer (NSCLC): Patients treated with platinum-based chemotherapy who had low muscle mass showed an approximately 2.5-fold increase in the risk of severe hematological toxicity. Low muscle mass has also been reported as an independent predictor of severe immune-related toxicities in patients receiving immunotherapy agents such as nivolumab.
Ovarian cancer: Low skeletal muscle radiodensity and a low subcutaneous adipose tissue index independently predicted severe adverse events and the need for treatment modifications.
Pancreatic and thyroid cancer: Some studies found no significant association between baseline low muscle mass and short-term dose modifications or adverse outcomes.
Across the literature there are both positive associations and null results, varying by tumor type, treatment class, and the specific body-composition metric used.
The review outlines a biologically plausible mechanism whereby reduced skeletal muscle lowers the distribution volume for hydrophilic agents (for example, some platinum compounds) and possibly for certain monoclonal antibodies. A smaller distribution volume could raise peak plasma concentrations after standard dosing, potentially increasing toxicity risk. While this pharmacokinetic rationale is coherent, the authors stress that current clinical evidence is heterogeneous and insufficient to definitively confirm causality.
The literature is limited by marked heterogeneity in several domains:
Body-composition metrics and definitions: Studies measured different parameters (muscle area, radiodensity, adipose indices) and applied inconsistent thresholds to define abnormal values.
Endpoints and toxicity assessment: Treatment tolerance was evaluated using diverse outcomes and timeframes, reducing comparability across studies.
Study design and confounding: Many reports lacked standardized adjustment for key confounders, and most evidence derives from retrospective or observational cohorts of varying size, limiting causal inference.
Inconsistency of findings: Some malignancies and treatments demonstrate associations, while others do not, making generalization premature.
Because of these limitations, the review treats existing findings as hypothesis-generating rather than practice-changing.
The review concludes that although the link between decreased skeletal muscle and heightened treatment toxicity is biologically plausible, current evidence is too heterogeneous to support routine use of body-composition assessment for dose individualization. Before recommending body composition for treatment planning, the field needs:
The authors indicate that, until such evidence accumulates, body-composition measures should be interpreted cautiously and primarily as drivers of further research rather than as determinants of routine dose modification.
Current research suggests a potential but unconfirmed association between adverse body composition (low muscle mass and poor muscle quality) and increased treatment-related toxicity across some cancer types and therapies. Reported associations include a higher risk of severe hematological toxicity with low muscle mass in NSCLC patients receiving platinum chemotherapy and associations between poor muscle radiodensity or low subcutaneous adipose tissue and severe adverse events in ovarian cancer. However, other tumor types have shown no association, and the overall evidence base is heterogeneous and limited by variable definitions, endpoints, and confounder control. The review calls for standardization, validation, and prospective investigation before body-composition assessment can be recommended for routine dose individualization or treatment planning in oncology.
Conflict of interest: The authors declared no competing interests in the source article.