Circadian rest-activity rhythm as a predictor of survival in metastatic colorectal cancer.

Abstract

e14006 Background: Experimental disruption of the Circadian Timing System (CTS) accelerates cancer progression. The relative amount of activity in-bed versus out-of-bed (I<O) was identified as a quantitative CTS estimate that predicted survival in two cohorts of patients with metastatic colorectal cancer (CI, CII). Methods: The independent prognostic value of I<O was investigated for Overall Survival (OS) and Progression-Free Survival (PFS) 1) in a new cohort of 142 patients (CIII) receiving circadian-based salvage treatment for metastatic colorectal cancer, and 2) in a pooled population of 436 patients from cohorts I-III. All patients had two-day rest-activity rhythm monitoring and then received a new treatment. Cohort-adjusted data were analyzed with log rank and multivariate Cox analyses. Results: Patients in CIII had poor prognosis disease compared to CI and CII, as assessed by prior chemotherapy (CIII, 69%; CI, 59.5%; CII, none), prior oxaliplatin (CIII, 55%; CII, none; CI, 2%) and/or irinotecan (CIII, 39.4%; CII, none; CI, 7%). The 273 male and 163 female patients in the pooled population had generally good performance status 0 (60.7%) or 1 (33.1%) and 51% had two or more metastatic sites. Following rest-activity rhythm determination, patients received a median of 8 chemotherapy courses. Median OS was 21.6 months [95% Confidence Limits, 17.8 to 25.5] in the patients with I<O above the cutoff median value of 97.5% as compared to 11.9 months [10.4 to 13.3] in those with a lower I<O (p from Log rank < 0.001). The adjusted relative risk related to I<O above cutoff was 0.587 [0.477 to 0.722] for earlier death (p<0.001) and 0.661 [0.542 to 0.807] for earlier progression (p <0.001). Conclusions: The circadian biomarker indicator I<O is a robust and independent quantitative long-term predictor of both OS and PFS in patients with metastatic colorectal cancer. Cancer patients with low I<O could potentially benefit from specific treatments for circadian disruption in order to enhance survival.