Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
JAMA Oncol. 2023 May 1;9(5):705-709. doi: 10.1001/jamaoncol.2022.7753.
Immune checkpoint blockade (ICB) has improved the survival of patients with advanced melanoma. Durable responses are observed for 40% to 60% of patients, depending on treatment regimens. However, there is still large variability in the response to treatment with ICB, and patients experience a range of immune-related adverse events of differing severity. Nutrition, through its association with the immune system and gut microbiome, is a poorly explored but appealing target with potential to improve the efficacy and tolerability of ICB.
To investigate the association between habitual diet and response to treatment with ICB.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study (the PRIMM study) was conducted in cancer centers in the Netherlands and UK and included 91 ICB-naive patients with advanced melanoma who were receiving ICB between 2018 and 2021.
Patients were treated with anti-programmed cell death 1 and anti-cytotoxic T lymphocyte-associated antigen 4 monotherapy or combination therapy. Dietary intake was assessed through food frequency questionnaires before treatment.
Clinical end points were defined as overall response rate (ORR), progression-free survival at 12 months (PFS-12), and immune-related adverse events that were grade 2 or higher.
There were a total of 44 Dutch participants (mean [SD] age, 59.43 [12.74] years; 22 women [50%]) and 47 British participants (mean [SD] age, 66.21 [16.63] years; 15 women [32%]). Dietary and clinical data were prospectively collected from 91 patients receiving ICB between 2018 and 2021 for advanced melanoma in the UK and the Netherlands. Logistic generalized additive models revealed positive linear associations between a Mediterranean dietary pattern that was high in whole grains, fish, nuts, fruit, and vegetables and the probability of ORR and PFS-12 (probability of 0.77 for ORR; P = .02; false discovery rate, 0.032; effective degrees of freedom, 0.83; probability of 0.74 for PFS-12; P = .01; false discovery rate, 0.021; effective degrees of freedom, 1.54).
This cohort study found a positive association between a Mediterranean diet, a widely recommended model of healthy eating, and response to treatment with ICB. Large prospective studies from different geographies are needed to confirm the findings and further elucidate the role of diet in the context of ICB.
免疫检查点阻断(ICB)改善了晚期黑色素瘤患者的生存。根据治疗方案的不同,40%至 60%的患者观察到持久的反应。然而,ICB 治疗的反应仍存在很大的变异性,患者会经历一系列不同严重程度的免疫相关不良事件。营养通过与免疫系统和肠道微生物群的关联,是一个探索不足但有吸引力的目标,具有提高 ICB 疗效和耐受性的潜力。
研究习惯性饮食与 ICB 治疗反应之间的关系。
设计、地点和参与者:这是一项多中心队列研究(PRIMM 研究),在荷兰和英国的癌症中心进行,纳入了 91 名接受 ICB 治疗的晚期黑色素瘤 ICB 初治患者,他们在 2018 年至 2021 年间接受了 ICB 治疗。
患者接受抗程序性细胞死亡 1 和抗细胞毒性 T 淋巴细胞相关抗原 4 单药或联合治疗。治疗前通过食物频率问卷评估饮食摄入。
临床终点定义为总缓解率(ORR)、12 个月无进展生存率(PFS-12)和 2 级或以上的免疫相关不良事件。
共有 44 名荷兰参与者(平均[SD]年龄,59.43[12.74]岁;22 名女性[50%])和 47 名英国参与者(平均[SD]年龄,66.21[16.63]岁;15 名女性[32%])。前瞻性收集了 2018 年至 2021 年间在英国和荷兰接受 ICB 治疗的晚期黑色素瘤患者的饮食和临床数据。逻辑广义加性模型显示,富含全谷物、鱼类、坚果、水果和蔬菜的地中海饮食模式与 ORR 和 PFS-12 概率呈正线性关系(ORR 概率为 0.77;P=0.02;假发现率为 0.032;有效自由度为 0.83;PFS-12 概率为 0.74;P=0.01;假发现率为 0.021;有效自由度为 1.54)。
这项队列研究发现,地中海饮食与 ICB 治疗反应之间存在正相关,地中海饮食是一种广泛推荐的健康饮食模式。需要来自不同地理位置的大型前瞻性研究来证实这些发现,并进一步阐明饮食在 ICB 背景下的作用。