THE ASSOCIATION BETWEEN THE CIRCADIAN MISALIGNMENT OF SERUM CORTISOL ACROPHASE AND SLEEP END TIME WITH CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY

초록

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of chemotherapy. No studies have yet investigated the relationship between circadian misalignment (CM) and CIPN. Methods: This prospective observational study recruited 39 breast cancer patients awaiting chemotherapy, of whom 23 were assessed for CM prior to chemotherapy. The CM was quantified by measuring the phase angle difference (PAD) of the acrophase of serum cortisol concentration and sleep end time assessed with actigraphy and sleep diary. CIPN was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN20 (EORTC QLQ-CIPN20) and the MD Anderson Symptom Inventory (MDASI) throughout the course of chemotherapy, at one month (T1) and at nine months (T2) after the completion of chemotherapy. Results: The assessment of CM revealed that the sleep end time of the high and low PAD groups were not statistically different, whereas the cortisol acrophase of the low PAD group was more advanced compared to the high PAD group (p<0.001). The low PAD group showed significantly higher EORTC QLQ-CIPN20 global and sensory scores compared to the high PAD group at T1 (both p < 0.001), while these scales decreased in the high PAD group after completion of chemotherapy. For the MDASI "numbness and tingling" item, a significant difference was observed between the low and high PAD groups across all time points (p=0.014). Discussion: While the high PAD group can be considered to have a phase relationship between biological and behavioral rhythms similar to the average population with a similar sleep placement, the low PAD group has a more delayed behavioral rhythm relative to the biological rhythm. The low PAD group can be interpreted as a population with a higher degree of circadian misalignment compared to the high PAD group. According to previous studies, circadian misalignment is associated with systemic inflammation, which may contribute to the worsening and persistence of CIPN observed in the low PAD group. Conclusions: The results of this study indicate that the low PAD group, which had a higher degree of CM, had a higher susceptibility to CIPN. By evaluating CM using objective measures and analyzing its association with CIPN, this study suggests that CM may contribute to the pathogenesis of CIPN.