Low fT3/fT4 Ratio as a Proxy for Muscle Wasting in Patients with Advanced Non-Small Cell Lung Cancer Treated with Pembrolizumab

Serena Eccher¹Marco Sposito¹Ilaria Trestini¹Ilaria Mariangela Scaglione¹Luca Pasqualin¹Daniela Tregnago¹Alice Avancini¹Jessica Insolda¹Linda Confortini¹Alessandra Dodi²Alessio Stefani³Marco Cintoni⁴Isabella Sperduti⁵Maria Cristina Mele⁴Fotios Loupakis⁶Marcello Tiseo⁷Emilio Bria^3,8Michele Milella¹Sara Pilotto^1*Lorenzo Belluomini¹

• ¹University of Verona, Verona, Italy
• ²Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
• ³Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy
• ⁴Policlinico Universitario Agostino Gemelli UOC Nutrizione Clinica, Rome, Italy
• ⁵IRCCS Istituto Nazionale Tumori Regina Elena, Rome, Italy
• ⁶3trees Healthcare, Viterbo, Italy
• ⁷Universita degli Studi di Parma, Parma, Italy
• ⁸Ospedale Fatebenefratelli Isola Tiberina - Gemelli Isola, Rome, Italy

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.: 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%. 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.