低维生素D症在癌症患者中可能产生负面的预后影响。维生素D在T细胞介导的免疫激活中发挥了重要作用。我们假设系统的补充维生素D可能会对接受免疫检查点抑制剂（ICI）治疗的癌症患者的临床结果产生影响。我们计划进行一项前瞻性观察性研究（PROVIDENCE），评估接受ICI治疗的晚期癌症患者的血清维生素D水平（队列1为治疗开始时，队列2为治疗期间）以及系统性补充对生存和毒性结果的影响。在一个探索性分析中，我们将队列1的临床结果与参与中心进行随访但未接受系统性维生素D补充的对照队列进行比较。总体上，我们在PROVIDENCE研究中招募了164名患者。队列1包括101名患者，其中94.1％在基线时血清维生素D不足（≤ 30 ng/ml），在3个月后的再评估中，有70.1％的患者通过胆钙化醇获得了足够的补充。队列2由63名患者组成，他们在免疫治疗开始后的中位时间3.7个月时评估了维生素D水平，没有患者的维生素D水平达到适当水平（> 30 ng/ml）。即使在队列2中，系统补充在3个月后的再评估中仍使77.8％的患者达到了适当水平。与238名未接受系统性维生素D补充的回顾性对照组患者相比，PROVIDENCE队列1显示出更长的总生存期（OS，p = 0.013），治疗失败时间（TTF，p = 0.017）和更高的疾病控制率（DCR，p = 0.016）。倒数概率治疗加权（IPTW）拟合的多变量Cox回归分析证实，与对照队列相比，PROVIDENCE队列1的死亡风险显著降低（HR 0.55，95％CI：0.34-0.90）和治疗中断风险显著降低（HR 0.61，95％CI：0.40-0.91）。在治疗过程中，PROVIDENCE队列1发生任何级别免疫相关不良事件（irAEs）的累积发生率高于对照队列。然而，与对照队列相比，队列1的患者甲状腺irAEs的所有级别风险显著降低（OR 0.16，95％CI：0.03-0.85）。PROVIDENCE研究表明了早期系统性维生素D补充对接受ICI治疗的晚期癌症患者结果的潜在积极影响，并支持足够补充作为可能的甲状腺irAEs预防措施。©2023. 作者们。

Hypovitaminosis D can have a negative prognostic impact in patients with cancer. Vitamin D has a demonstrated role in T-cell-mediated immune activation. We hypothesized that systematic vitamin D repletion could impact clinical outcomes in patients with cancer receiving immune-checkpoint inhibitors (ICIs).We planned a prospective observational study (PROVIDENCE) to assess serum vitamin D levels in patients with advanced cancer receiving ICIs (cohort 1 at treatment initiation, cohort 2 during treatment) and the impact of systematic repletion on survival and toxicity outcomes. In an exploratory analysis, we compared the clinical outcomes of cohort 1 with a control cohort of patients followed at the participating centers who did not receive systematic vitamin D repletion.Overall, 164 patients were prospectively recruited in the PROVIDENCE study. In cohort 1, consisting of 101 patients with 94.1% hypovitaminosis (≤ 30 ng/ml) at baseline, adequate repletion with cholecalciferol was obtained in 70.1% at the three months re-assessment. Cohort 2 consisted of 63 patients assessed for vitamin D at a median time of 3.7 months since immunotherapy initiation, with no patients having adequate levels (> 30 ng/ml). Even in cohort 2, systematic supplementation led to adequate levels in 77.8% of patients at the three months re-assessment. Compared to a retrospective control group of 238 patients without systematic vitamin D repletion, PROVIDENCE cohort 1 showed longer overall survival (OS, p = 0.013), time to treatment failure (TTF, p = 0.017), and higher disease control rate (DCR, p = 0.016). The Inverse Probability of Treatment Weighing (IPTW) fitted multivariable Cox regression confirmed the significantly decreased risk of death (HR 0.55, 95%CI: 0.34-0.90) and treatment discontinuation (HR 0.61, 95%CI: 0.40-0.91) for patients from PROVIDENCE cohort 1 in comparison to the control cohort. In the context of longer treatment exposure, the cumulative incidence of any grade immune-related adverse events (irAEs) was higher in the PROVIDENCE cohort 1 compared to the control cohort. Nevertheless, patients from cohort 1 experienced a significantly decreased risk of all grade thyroid irAEs than the control cohort (OR 0.16, 95%CI: 0.03-0.85).The PROVIDENCE study suggests the potential positive impact of early systematic vitamin D supplementation on outcomes of patients with advanced cancer receiving ICIs and support adequate repletion as a possible prophylaxis for thyroid irAEs.© 2023. The Author(s).