Skeletal muscle adaptations in patients with lung cancer: Longitudinal observations from the whole body to cellular level

Background Cancer and its treatment can adversely affect skeletal muscle, impacting physical function, treatment response and survival. No studies, however, have comprehensively characterized these muscle adaptations longitudinally in human patients at the cellular level. Methods We examined skeletal muscle size and function from the whole body to the sub‐cellular level in 11 patients with non‐small cell lung cancer (NSCLC; 6 male/5 female, mean age 58 ± 3 years) studied over a 2‐month observation period starting during their first cycle of standard of care cancer treatment and in 11 age‐ and sex‐matched healthy controls (HC) without a current or past history of cancer. Biopsies of the vastus lateralis were performed to assess muscle fibre size, contractility and mitochondrial content, along with assessments of physical function, whole muscle size and function, and circulating cytokines. Results Body weight, composition and thigh muscle area and density were unaltered over time in patients with NSCLC, while muscle density was lower in patients with NSCLC versus HC (P = 0.03). Skeletal muscle fibre size decreased by 18% over time in patients (all P = 0.02) and was lower than HC (P = 0.02). Mitochondrial fractional area and density did not change over time in patients, but fractional area was lower in patients with NSCLC compared with HC (subsarcolemmal, P = 0.04; intermyofibrillar, P = 0.03). Patients with NSCLC had higher plasma concentrations of IL‐6 (HC 1.40 ± 0.50; NSCLC 4.71 ± 4.22; P