Introduction: Circadian rhythms are evolutionarily conserved organismal processes that involve daily oscillations of biological machineries including those involved in cancer progression and immune response. Emerging research suggests that the efficacy of cancer immunotherapy may vary by time of treatment. Chronoimmunotherapy has not been studied in gastrointestinal (GI) cancers.
Methods: This was a retrospective study of patients with GI cancers who received immunotherapy (nivolumab, pembrolizumab, or atezolizumab) from 2017 to 2022 at a single, academic cancer center, Rush University Medical Center (Chicago, IL). Patients were excluded if they received less than 2 infusions or if their disease burden was not assessed at a 2-3 month follow up. The primary outcome was tumor regression, defined as evidence of decreased tumor burden on radiographic imaging confirmed by the treating oncologist. Patients were divided into two groups; those that received 50% or more infusions after noon and those that did not. We used chi-square analysis to compare disease regression between groups.
Results: Between 2017 and March 2022, we identified 63 GI cancer patients at Rush University Medical Center who were treated with immunotherapy, of which 43 patients had enough data for analysis and were included in this study. The median age was 66.7 years and 63% of patients were female. There was a trend towards a higher incidence of tumor regression in the morning vs. afternoon group [(40% (9/21) vs. 18% (4/22), respectively, P=0.078].
Discussion: Immunotherapy is becoming more widely used in multiple GI cancer types. We found a trend towards a higher incidence of tumor regression based on the timing of immunotherapy in GI cancers. The findings are consistent with results from previous studies in other tumor types (i.e. melanoma, lung cancer), where administration of immunotherapy earlier in the day was associated with better outcomes. Larger studies will be needed to confirm these findings and to apply the concept of chronoimmunotherapy in GI cancers.
