Clinical mechanism of muscle mass loss during neoadjuvant chemotherapy in older patients with esophageal cancer: a prospective cohort study

In older patients with locally advanced esophageal cancer (LAEC), loss of skeletal muscle mass during neoadjuvant chemotherapy (NAC) is associated with poor clinical outcomes. This study aimed to investigate factors associated with loss of skeletal muscle mass during NAC in older patients with LAEC. This was a single-center exploratory prospective cohort study. Consecutive patients aged ≥65 years with LAEC scheduled for curative esophagectomy after NAC were enrolled between October 2021 and December 2023. As a primary endpoint, loss of skeletal muscle mass index (ΔSMI: pre-NAC minus post-NAC value) was calculated from computed tomography images before and after NAC. Significant pre-NAC and during-NAC factors with ΔSMI were detected with a multivariate regression model. Statistical significance was considered as two-tailed P <0.05. A total of 69 patients were analyzed. The mean age was 72.9 years, and 53 (77%) were male. Mean SMI before and after NAC was 43.1 and 40.9 cm2/m2, and mean ΔSMI was 2.2 cm2/m2. In multivariate analysis, ΔSMI was associated with increased sitting time during NAC (per 1 min/day, adjusted coefficient 0.007, 95% confidence interval [CI] 0.001 to 0.013, P = 0.016), decreased Geriatric Nutritional Risk Index during NAC (per 1 score, adjusted coefficient -0.146, 95% CI -0.213 to -0.013, P = 0.002), and worsening decreased appetite during NAC (vs. no worsening, adjusted coefficient 1.571, 95% CI 0.279 to 2.862, P = 0.018). It was hypothesized that the inactivity-related mechanism and malnutrition-related mechanism are important for skeletal muscle mass loss during NAC in older patients with LAEC.