Circadian rhythm in rest and activity: a biological correlate of quality of life and a predictor of survival in patients with metastatic colorectal cancer

摘要

The rest/activity circadian rhythm (CircAct) reflects the function of the circadian timing system (CTS). In a prior single-institution study, the extent of CircAct perturbation independently predicted for survival and tumor response in 192 patients receiving chemotherapy for metastatic colorectal cancer (MCRC). Moreover, the main CircAct parameters correlated with several quality of life (HRQoL) scales. In this prospective study we attempted to extend these results to an independent cohort of chemotherapy-naïve MCRC patients participating in an international randomized phase III trial (EORTC 05963).Patients were randomized to receive chronomodulated or conventional infusion of 5-fluorouracil, leucovorin and oxaliplatin as first line treatment for MCRC.Patients from nine institutions completed the EORTC QLQ-C30, and wore a wrist-accelerometer (actigraph) for 3 days before chemotherapy delivery. Two validated parameters (I<O and r24) were used to estimate CircAct.Of 130 patients with baseline CircAct assessments, 96 had baseline HRQoL data. I<O was confirmed to correlate with global quality of life, physical functioning, social functioning, fatigue and appetite loss (r>|0.25|, p<0.01). I<O further independently predicted for overall survival with a Hazard Ratio of 0.94 (p<0.0001).The associations between CircAct parameters, HRQoL and survival that were demonstrated in this international study involving previously untreated MCRC patients, confirm prior single-institution findings in mostly pretreated MCRC patients. The circadian timing system constitutes a novel therapeutic target. Interventions that normalize circadian timing system dysfunction may impact quality of life and survival in cancer patients