Sarcopenia, elevated body mass index, and platinum-associated adverse events in patients with lung cancer

Abstract

Background: Patients with sarcopenia and elevated body mass index (BMI) are at high risk of platinum-associated adverse events (AEs). This study examines the association between sarcopenia, BMI, and AEs in patients with non-small cell lung cancer (NSCLC). Methods: Retrospective cohort study including adult patients with NSCLC who started cisplatin or carboplatin between 2015-2022. Sarcopenia was defined on computed tomography (CT) using sex-specific cutoffs for skeletal muscle index. We determined the association between CT-defined sarcopenia in patients with normal BMI ( 25 kg/m2) and elevated BMI (≥ 25 kg/m2) and ≥ grade 2 AEs (including anemia, thrombocytopenia, neutropenia, and creatinine increased), chemotherapy discontinuation and mortality within 90 days using a Fine-Gray subdistribution hazard model. The association between receiving an excess carboplatin dose and AEs was evaluated. Results: Of 604 included patients, mean age was 66±10 years, 307 were female (51%), and 167 (28%) had sarcopenia. Sarcopenia and elevated BMI (N = 67) was associated with an increased risk of grade ≥ 2 anemia (subdistribution hazard ratio [sHR] 1.64, 95% confidence interval [CI] 1.17-2.29, P = 0.004), thrombocytopenia (sHR 2.25, 95%CI 1.16-4.36, P = 0.016), and creatinine increased (sHR 2.72, 95%CI 1.45-5.13, P = 0.002). Sensitivity analyses demonstrated that patients whose Cockcroft-Gault based glomerular filtration rate (GFR) dictated a carboplatin dose ≥ 25mg higher than CKD-EPI GFR were at significantly higher risk of grade ≥ 2 AEs and chemotherapy discontinuation. Conclusions: Combined CT-defined sarcopenia with elevated BMI is associated with an increased risk of platinum-associated AEs in patients with NSCLC; this may be due to GFR misestimation in patients with low muscle mass and elevated BMI.