P17.31.A PRE-TREATMENT SARCOPENIA IS A RISK FACTOR FOR DEVELOPING CLINICALLY RELEVANT CHEMOTHERAPY-INDUCED PERIPHERAL NEUROTOXICITY

Abstract BACKGROUND Sarcopenia, characterized by low muscle mass, is commonly seen in cancer patients. Further, it is an independent predictor of chemotherapy toxicity and may also influence the pharmacokinetics of anticancer drugs. However, its association with chemotherapy-induced peripheral neurotoxicity (CIPN) remains unknown. MATERIAL AND METHODS Material and methods: A single-institution, prospective observational study was conducted on newly diagnosed cancer patients who were treated with brentuximab vedotin (n=50), oxaliplatin (n=44), or paclitaxel (n=11). Patients were evaluated before treatment (T0) and after completing treatment (T1). Sarcopenia was analyzed using the skeletal muscle index (SMI) according to previously defined cutoff points at the third lumbar vertebra of re-treatment computerized tomography (CT) or PET/CT scans. The extent of CIPN was evaluated using clinical scales (TNSc and NCI-CTCv5) and nerve conduction studies. Blood levels of neurofilament (NfL), myostatin and albumin were determined at T0 and T1. Clinically relevant CIPN (CR-CIPN) was defined as > grade 2. RESULTS Results: A total of 105 patients (55 males, 52.4%; median age: 55 years [range: 21-78]) were included. Half of the patients (n = 50; 47.6%) had sarcopenia at baseline (T0). Serum myostatin levels were significantly lower in patients with sarcopenia compared to those without (737.90 pg/mL vs. 1308.00 pg/mL, p = 0.012), and correlated with skeletal muscle index (SMI) (r = 0.440, p = 0.009). Chemotherapy-induced peripheral neuropathy (CIPN) occurred in 89 patients (84.7%), with 39% developing clinically relevant CIPN (CR-CIPN), including 33.3% with grade 2 and 5.7% with grade 3 symptoms. A significant increase in neurofilament light chain (NfL) levels (T0: 14.52 pg/mL vs. T1: 82.58 pg/mL; p < 0.001) and Total Neuropathy Score - clinical (TNSc) scores (T0: 0 [0-12] vs. T1: 6 [0-17]; p < 0.001) was observed. Patients with CR-CIPN had a higher prevalence of pre-treatment sarcopenia (63.4% vs. 37.5%; p = 0.016). No significant differences in pre-treatment body mass index (BMI) or serum biomarkers were observed. Multivariate analysis identified sarcopenia as an independent risk factor for CR-CIPN (HR: 3.7; 95% CI: 1.25-10.91; p=0.018). CONCLUSION Sarcopenia before treatment is associated with the development of moderate-severe CIPN. Using pre-chemotherapy CT scan can help identify individuals at higher risk of CR-CIPN. Studies on CIPN should consider pre-treatment sarcopenia as a risk factor.