CANCER treatment timing may influence the effectiveness and safety of systemic therapy, according to a systematic review that examined the impact of treatment timing, seasonality, latitude, vitamin D status, and circadian rhythm on outcomes in patients with solid tumours. While evidence was strongest for chronomodulated chemotherapy, the authors concluded that prospective randomised studies are needed before broader implementation of timing-based treatment strategies.
The review followed Preferred Reporting Items for Systematic Reviews and Meta Analyses 2020 guidance and searched four databases from inception to January 20, 2026, alongside oncology conference proceedings and trial registries. Eligible studies included randomised trials, observational cohorts, and meta-analyses investigating treatment timing, season or latitude related factors, serum 25 hydroxyvitamin D concentrations, or objective measures of circadian disruption.
In total, 35 studies met the inclusion criteria, including six randomised trials, two patient level meta-analyses, five prospective cohort studies, and 22 retrospective cohort studies. Outcomes included overall survival, progression free survival, treatment response, and treatment related toxicity. Owing to substantial clinical and methodological heterogeneity, the findings were synthesised qualitatively.
Across the included studies, chronomodulated chemotherapy consistently reduced treatment related toxicity and, in some studies, improved response or time to progression. However, effects on survival were inconsistent and appeared to differ according to sex.
Earlier administration of immune checkpoint inhibitors, typically during the morning or early daytime, was associated with longer overall survival and progression free survival in predominantly retrospective studies. The authors noted that these findings should be considered hypothesis generating until confirmed in prospective trials.
Seasonal and geographical analyses generally linked winter treatment and higher latitude with poorer outcomes, although the observational nature of these studies limited causal interpretation. Higher vitamin D concentrations and supplementation during immunotherapy were also associated with improved survival, although these associations may have reflected baseline health status and other prognostic factors. Objective measures of circadian disruption were consistently associated with poorer prognosis.
The review suggested that treatment timing, circadian rhythm integrity, seasonal variation, latitude related sunlight exposure, and vitamin D status may all influence outcomes following systemic cancer therapy. However, the strength of evidence varied across exposure types.
They recommended prospective randomised studies to evaluate pragmatic interventions, including structured immune checkpoint inhibitor scheduling and vitamin D assessment and correction, before these approaches are incorporated into routine oncology practice.
Reference
Ghidini A et al. Latitude, seasonality, and circadian determinants of outcomes of systemic cancer therapy: Evidence from chemotherapy, immunotherapy, and chemo-immunotherapy combinations. A systematic review. Crit Rev Oncol Hematol. 2026 Aug 1:226:105509.
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