ABSTRACT
INTRODUCTION: Vitamin D3, which originates from cholesterol, exerts its influence on immune cells and potentially cancer cells via the metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D3), impacting their proliferation, differentiation, and apoptosis. An umbrella review was conducted to evaluate the potential protective effect of vitamin D3 intake and serum levels on the incidence and mortality of cancer. MATERIAL AND METHODS: A systematic search was conducted in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE databases from their inception to October 1, 2023. We included meta-analyses of observational or randomized clinical trials that compared interventions (vitamin D3 intake) or blood levels in a healthy population, with cancer incidence or mortality as outcomes. The grading of evidence certainty followed established criteria, including strong, highly suggestive, suggestive, weak, or not significant. RESULTS: A total of 71 systematic reviews were included. Strong evidence indicated that vitamin D3 supplementation reduced total cancer mortality (odds ratio [OR], 0.9 [95% CI, 0.87-0.92]; P < 0.01). In the context of site-specific cancers, there exists highly suggestive evidence pointing towards the potential prevention of head and neck, breast, colorectal, lung, and renal cell cancers through the intake of vitamin D3. Furthermore, strong evidence suggests that maintaining sufficient levels of vitamin D3 may effectively lower the risk of renal cell and thyroid cancer (OR = 0.76 [95%CI 0.64-0.88]). CONCLUSIONS: There is significant evidence that vitamin D3 intake may reduce the incidence of some cancers. Routine assessments to ensure sufficient levels of vitamin D3 and administering supplements to address deficiencies may serve as crucial preventive measures for healthcare systems.
ABSTRACT
INTRODUCTION: The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts. MATERIALS AND METHODS: This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches. RESULTS: The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01). DISCUSSION: Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.