Low fT3/fT4 ratio as a proxy for muscle wasting in patients with advanced non-small cell lung cancer treated with pembrolizumab

Background Loss of skeletal muscle mass may serve as a valuable indicator of treatment efficacy and survival in individuals with lung cancer undergoing immunotherapy. This investigation sought to pinpoint accessible markers that could reflect the presence of muscle degradation. Methods A retrospective study was conducted on patients with advanced non-small cell lung cancer (NSCLC) who received first-line pembrolizumab therapy from June 2018 to September 2021. Data collected included computed tomography (CT)-based body composition, clinical and radiological characteristics, along with thyroid function tests (free triiodothyronine [fT3] and free thyroxine [fT4]). Predictive factors were evaluated using multivariate logistic regression models. Results Among 31 patients, muscle wasting was observed in 58.1%. Performance Status (PS) emerged as a strong predictor (p=0.005), and a significant link was also found between muscle depletion and fT3/fT4 ratio (p=0.0296). After adjusting for PS, the association with the hormone ratio remained suggestive though not statistically definitive (p=0.091). ROC curve analysis identified a threshold value of 2.84 for fT3/fT4 ratio, which best differentiated patients at higher versus lower risk of muscle loss. Notably, 77.3% of individuals with muscle wasting had a ratio below this cut-off, compared to only 14.3% of those with higher ratios (p=0.006). While no significant correlation was found between the hormone ratio and progression-free survival (PFS), a meaningful association with overall survival (OS) was observed (p=0.032). Conclusions Despite the limited sample size, fT3/fT4 ratio appears to be a promising and accessible biomarker for identifying muscle wasting, which may be linked to diminished treatment response and shorter survival in patients with NSCLC.