Seasonal variations in overall survival and vitamin D status in a UK pan-cancer cohort receiving checkpoint inhibitors

Abstract Background There is conflicting evidence as to whether the season of immune checkpoint inhibitor (ICI) initiation influences overall survival (OS) in melanoma. Independently of season, vitamin D (VitD) status is linked to ICI outcomes across cancer types. This study investigated seasonal variations in VitD status and examined associations of VitD and season of ICI initiation with OS for different ICIs and cancer types in a UK cohort. Methods A single-site retrospective review was conducted in which patients were categorized by ICI initiation (October–March vs. April–September and December–February vs. June–August) and VitD status (sufficient > 50, insufficient 25–50 vs. deficient < 25 nmol/L). Kaplan–Meier and Cox analyses were used to estimate median OS (mOS), 1-year survival and adjusted hazard ratios (aHR) of OS. Results Among 4,329 patients (2191 events) treated between 2018 and 2023, ICI initiation in April-September vs. October–March was not associated with OS (aHR 1.00; 1-year survival 64.9% vs. 65.0%; and mOS 21.3 vs. 21.8 months). June–August versus December-February initiation was associated with longer OS for nivolumab and ipilimumab (aHR 0.64) and small cell lung cancer (aHR 0.52) but not other ICIs/cancers. VitD deficiency among 1,206 patients ranged from 28.4% in March to 3.5% in August. VitD status was associated with OS (aHR insufficient 1.64; aHR deficient 2.38). For VitD-sufficient patients, season of initiation was not associated with OS. Conclusion ICI initiation season was not consistently associated with OS, which may indicate that the observed seasonal VitD variations were insufficient to influence ICI effectiveness, or the previously reported VitD-OS association may be confounded. Regimen/disease-specific effects merit further investigation.