Circulating vitamin D level before initiating chemotherapy impacts on the time-to-outcome in metastatic colorectal cancer patients: systematic review and meta-analysis

Background Vitamin D (VD) is implicated in various health conditions, including colorectal cancer (CRC). To inves tigate potential relationships between pre-chemotherapy VD levels and the time-to-outcome in metastatic CRC patients, we conducted a systematic review and meta-analysis. Methods Following the PRISMA 2020 guidelines, we performed thorough searches in PubMed/MEDLINE and Sco pus/ELSEVIER databases (covering the years 2002 to 2022). Inclusion criteria mandated studies to report on individu als aged 18 years and above with histologically confirmed stage IV CRC. Additionally, studies needed to provide data on VD levels before chemotherapy, along with hazard ratios (HR) and 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS). Five articles were identified with the aim of establishing a combined risk estimate for death and progression based on pre-chemotherapy VD levels. Heterogeneity among studies and publica tion bias were evaluated using Tau2, I2 statistics, and a Funnel plot. Results Although no significant heterogeneity was observed in time-to-outcome among the selected studies, varia tions in technical assessments and serum VD concentration measurements were noted. The pooled analysis, involving 1712 patients for OS and 1264 patients for PFS, revealed a 47% increased risk of death (HR: 1.47, 95% CI: 1.21–1.79) and a 38% increased risk of progression (HR: 1.38, 95% CI: 1.13–1.70) for patients with lower VD levels, as indicated by fixed-effects models. Conclusions Our results emphasize the adverse effects of low VD concentration on the time-to-outcome in meta static CRC patients. This underscores the importance of investigating VD supplementation as an innovative approach in this clinical setting to enhance patient outcomes. Keywords Metastatic colorectal cancer, Vitamin D, Prognosis, Meta-analysis, Overall survival, Progression-free survival