Early-day may improve survival outcomes in non-small cell lung cancer, but clinical adoption remains unsettled.
Evidence
This review synthesizes circadian-mechanism data and clinical trial evidence on time-of-day immunochemotherapy in NSCLC and other cancers.
Caveat
The abstract names patient circadian heterogeneity, oncology-clinic logistics, and limited biomarker validation as major barriers requiring multicenter validation.
Simplified
Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases and remains a leading cause of cancer mortality worldwide. Pathophysiologically, NSCLC arises from genetic alterations such as EGFR, KRAS, and ALK mutations, which drive dysregulated signaling, uncontrolled proliferation, and immune evasion. Standard treatments include surgery, radiotherapy, platinum-based chemotherapy, and immunotherapy with PD-1/PD-L1 inhibitors, yet survival outcomes remain suboptimal. Emerging evidence suggests that circadian biology influences therapeutic efficacy, with time-of-day (ToD) offering a novel approach to optimize outcomes. Mechanistically, regulate immune cell trafficking, cytokine release, and drug metabolism, thereby modulating treatment response and toxicity. Clinical trials in NSCLC demonstrate that early-day administration of immunochemotherapy improves progression-free and overall survival compared to late dosing. Similar chronotherapy benefits have been reported in colorectal, breast, pancreatic, and hepatocellular cancers, underscoring broad translational relevance. Despite promise, challenges include patient heterogeneity in circadian rhythms, logistical barriers in oncology clinics, and limited biomarker validation. Future strategies should prioritize multicenter validation, integration of chronobiological profiling, and exploration of combination therapies. Cost-effectiveness analyses, awareness campaigns, and clinical drives to evaluate safety and adherence will be essential to establish trust and optimize outcomes.
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Circadian Biology