Sarcopenia in Patients With Cancer and Its Association With Chemotherapy-Induced Peripheral Neurotoxicity

Chemotherapy-induced peripheral neurotoxicity (CIPN) is the most common neurologic complication of cancer treatment. Sarcopenia, characterized by muscle mass loss, has been associated with treatment-related toxicity, but its association with CIPN remains unclear. We aimed to assess the association of pretreatment sarcopenia with the development of CIPN.

A single-center, prospective observational study at the Hospital Universitari de Bellvitge-Institut Català d'Oncologia was conducted on patients with cancer scheduled to receive brentuximab vedotin (BV), oxaliplatin (OXA), or paclitaxel (PTX). A pretreatment CT or PET-CT (≤30 days) was required. Sarcopenia was assessed using the skeletal muscle index at the third lumbar vertebra. Patients were evaluated before (T0) and after (T1) chemotherapy treatment. All patients were assessed using the Total Neuropathy Score-clinical version (TNSc) and Common Terminology Criteria for Adverse Events (CTCAE) at T0 and T1. Nerve conduction studies (NCS) and blood measurements (neurofilament [NfL], myostatin, and albumin) were conducted at the same time points. Clinically relevant (CR) CIPN was defined as CTCAE grade ≥2. Associations were analyzed using multivariate logistic regression.

A total of 105 patients (47.6% female; median age 55 years) were studied. Before treatment (T0), 47.6% of patients had sarcopenia. CIPN occurred in 84.7% of patients, with CR-CIPN observed in 39% (33.3% grade 2; 5.7% grade 3). At T1, NfL and TNSc scores increased significantly, while distal sensory and motor NCS amplitudes decreased. Sarcopenia was more common in patients developing CR-CIPN (61.9% vs 38.1%; p = 0.028). Multivariate analysis identified sarcopenia as an independent risk factor of CR-CIPN (odds ratio [OR] 2.5; 95% CI 1.07-5.83; p = 0.033), and patients receiving microtubule-based agents-PTX (OR 0.17, 95% CI 0.03-0.92, p = 0.04) or BV (OR 0.37, 95% CI 0.15-0.90, p = 0.027)-had lower odds of CR-CIPN compared with those receiving OXA.

Pretreatment sarcopenia is associated with 2.5-fold higher odds of moderate-to-severe CIPN. Assessing sarcopenia using routine prechemotherapy imaging techniques can help identify individuals at higher risk of CR-CIPN.