Longitudinal Associations of Oxaliplatin Treatment With Chemotherapy-Induced Peripheral Neuropathy in Colorectal cancer Survivors up to 2 Years Post-Treatment.

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially long-term consequence of oxaliplatin-based chemotherapy for colorectal cancer (CRC). Oxaliplatin dosing is based on body surface area (BSA), but lean body mass (LBM) may influence susceptibility to long-term CIPN. We examined associations between oxaliplatin treatment and CIPN up to 2 years post-treatment and whether LBM modified these associations. In a prospective cohort, we analysed 106 stage II-III CRC patients treated with adjuvant CAPOX. Data on oxaliplatin treatment were obtained from medical records. CIPN during treatment was graded with the CTCAE, and patient-reported CIPN was assessed by the EORTC QLQ-CIPN20 questionnaire at diagnosis and at 6 weeks and 6, 12, and 24 months post-treatment. LBM was derived from diagnostic CT scans, and sarcopenia was defined using sex-specific skeletal muscle index cut-offs. Longitudinal associations were analysed through confounder-adjusted linear mixed models. Effect modification by LBM and sarcopenia was examined by stratified analyses (median-split) and interaction tests. Higher cumulative oxaliplatin dose (β per 0.5 SD 2.91, 95% CI 1.22-4.59), relative oxaliplatin dose intensity (3.15, 1.2-5.25), and initial dose (2.21, 0.46-3.95) were longitudinally associated with higher CIPN summary scores. Patients with grade 2/3 CIPN had higher post-treatment CIPN scores (5.82; 0.63-11.01) than those with grade 1. Associations were generally stronger in patients with low LBM or sarcopenia, although interaction tests were not statistically significant. In conclusion, higher oxaliplatin exposure and CIPN during treatment were associated with greater long-term CIPN burden. Patients with low LBM or sarcopenia may be particularly vulnerable under current BSA-based dosing.