Mid-thigh muscle thickness measured on lateral femur radiographs as a surrogate marker of low muscle mass for sarcopenia screening in patients with cancer

Background Sarcopenia, a skeletal muscle disorder characterized by muscle mass loss, is common in cancer patients and associated with increased drug toxicity, complications, and mortality. Current diagnostics are resource-intensive. This study investigates whether mid-thigh muscle thickness (MTH) measured on lateral femur X-rays can serve as a surrogate marker of low muscle mass. Methods A single-centre, cross-sectional diagnostic study involving 136 cancer patients was conducted at a Malaysian tertiary hospital (February 2020–November 2022). Sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, combining handgrip strength and skeletal muscle index (SMI) derived from CT scans at L3 level. Three MTH values from X-rays (Three perpendicular lines were drawn: at 5 cm proximal to MTH (MTH1), at the mid-thigh (MTH), and 5 cm distal to MTH (MTH2) to this point). Multivariable logistic regression was used to assess whether MTH discriminated low muscle mass independently of BMI. The three MTH values were analysed unadjusted and indexed to BMI, together with BMI alone, against low L3 CT SMI using receiver operating characteristic (ROC) analysis to derive sex-specific cut-offs. In a secondary analysis, sex-specific sensitivity, specificity, PPV, NPV and accuracy were calculated for low handgrip strength combined with the derived cut-off against EWGSOP2-defined sarcopenia (L3 CT skeletal muscle index), recognising that both definitions share the handgrip component. Results In multivariable analysis, MTH2 remained an independent predictor of low muscle mass after adjustment for BMI in men (OR 0.204, p = 0.001), whereas MTH did not in women (OR 0.456, p = 0.115). In all patients, MTH × BMI had the highest AUC (83.5%), above BMI alone (82.3%). In men, MTH2 × BMI performed best with an AUC of 86.6% where a cut-off of 91.5 cmkg/m 2 gave a sensitivity of 87.1% and specificity of 72.5%. In women, BMI alone performed best with an AUC of 89.2% where a cut-off of 23.70 kg/m 2 gave a sensitivity of 90.9% and specificity of 79.1%. When combined with handgrip strength and compared against EWGSOP2-defined sarcopenia, sensitivity and specificity were 82.6% and 89.6% in men, and 89.5% and 97.8% in women. Conclusion This study shows that in men, MTH2 × BMI from lateral femur radiographs is a promising low-radiation screening measure for identifying low muscle mass where CT is not available. Combined with handgrip strength, it may serve as a screening tool for sarcopenia in male cancer patients. In women, BMI alone performed as well as the radiographic indices. These cut-offs are exploratory, having been derived and evaluated in the same single-centre cohort, and require external validation.