体重指数 (BMI) 与胰腺导管腺癌 (PDA) 生存率的关联在文献中存在很大差异，这可能是由于患者群体的异质性和回顾性分析所致。此外，BMI 可能不足以描述身体成分（即形态组学；包括皮下和内脏脂肪、肌肉和筋膜），而身体成分可能具有独立的生物学作用并与生存相关。 研究 BMI 和形态组学与转移性生存和代谢组学的关联PDA。这项队列研究前瞻性地收集了 3 期试验 (Avenger500) 的患者数据、影像学和血清，该试验研究了 5-氟尿嘧啶、亚叶酸、奥沙利铂和伊立替康 (FOLFIRINOX) 与改良 FOLFIRINOX 加 devimistat 的疗效和安全性。该随机试验招募了 2018 年至 2020 年间来自欧洲、以色列、韩国和美国的 528 名未经化疗的转移性 PDA 患者。在本研究中，对 L1 至 L4、T10 至 T12 椎骨水平的符合方案的患者进行了评估。数据分析发生于2023年1月至2024年4月。患者数据由临床工作人员收集。从基线成像中分析形态组学。从基线血清中提取代谢物。多方面的统计方法评估了 BMI 和形态组学与无进展生存期 (PFS) 和总生存期 (OS) 的关联。还研究了形态组学与代谢物的关联。 在 528 名初始患者中，476 名（中位 [IQR] 年龄，63 [56-68] 岁；280 名男性 [58.8%]；中位 [IQR] BMI，25.0 [22.1-25.9] ）对于本研究是可评估的。 BMI（肥胖[≥30]与正常[18.5-24.9]相比）与OS无关（风险比[HR]，0.90；95% CI，0.67-1.22；趋势P = .33）。更多的皮下脂肪与更长的 OS 相关（HR，0.62；95% CI，0.41-0.94；趋势 P = .02）。较高的内脏脂肪密度与较短的 PFS（HR，1.74；95% CI，1.23-2.48；P for trend = .002）和 OS（HR，1.50；95% CI，1.12-2.00；P for trend = .008）相关）。较高的肌肉与筋膜比率与较长的 PFS（HR，0.58；95% CI，0.40-0.84；P 趋势 = .005）和 OS（HR，0.56；95% CI，0.41-0.75；P 表示趋势）相关。趋势 = 1.7 × 10-4)。皮下脂肪与长链脂肪酸代谢呈正相关，包括降植烷酸、癸酰肉碱、癸烯酰肉碱和辛酰肉碱。肌肉到筋膜与乙酰肌肽等代谢物呈正相关（β = 0.34；95% CI，0.21-0.47；P = 1.27 × 10-6）。在转移性PDA患者的队列研究中，BMI与生存无关。较高的内脏脂肪密度、皮下脂肪面积和肌肉筋膜比与独立于体重指数的生存相关。后两者与较高水平的动物产品代谢相关。这些发现可能成为预测和干预以提高 PDA 患者生存率的新焦点。

Associations of body mass index (BMI) with survival in pancreatic ductal adenocarcinoma (PDA) have substantial variability in literature, potentially due to heterogeneous patient populations and retrospective analyses. Additionally, BMI may inadequately describe body composition (ie, morphomics; including subcutaneous and visceral fats, muscle, and fascia), which might have independent biological roles and associations with survival.To study the associations of BMI and morphomics with survival and metabolomics in metastatic PDA.This cohort study prospectively collected patient data, imaging, and serum on the phase 3 trial (Avenger500), which investigated the efficacy and safety of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) versus modified FOLFIRINOX plus devimistat. The randomized trial accrued 528 patients with chemotherapy-naive, metastatic PDA from Europe, Israel, Korea, and the US between 2018 and 2020. In the present study, per-protocol patients with L1 to L4, T10 to T12 vertebral levels were evaluated. Data analysis occurred from January 2023 to April 2024.Patient data were collected by clinical staff. Morphomics were analyzed from baseline imaging. Metabolites were extracted from baseline serum.A multifaceted statistical approach evaluated associations of BMI and morphomics with progression-free survival (PFS) and overall survival (OS). Associations of morphomics with metabolites were also studied.Of the 528 initial patients, 476 (median [IQR] age, 63 [56-68] years; 280 male [58.8%]; median [IQR] BMI, 25.0 [22.1-25.9]) were evaluable for the present study. BMI (obese [≥30] compared with normal [18.5-24.9]) was not associated with OS (hazard ratio [HR], 0.90; 95% CI, 0.67-1.22; P for trend = .33). More subcutaneous fat was associated with longer OS (HR, 0.62; 95% CI, 0.41-0.94; P for trend = .02). Higher visceral fat density was associated with shorter PFS (HR, 1.74; 95% CI, 1.23-2.48; P for trend = .002) and OS (HR, 1.50; 95% CI, 1.12-2.00; P for trend = .008). A higher muscle-to-fascia ratio was associated with longer PFS (HR, 0.58; 95% CI, 0.40-0.84; P for trend = .005) and OS (HR, 0.56; 95% CI, 0.41-0.75; P for trend = 1.7 × 10-4). Subcutaneous fat was positively associated with long-chain fatty acid metabolism including pristanic acid, decanoylcarnitine, decenoylcarnitine, and octanoylcarnitine. Muscle-to-fascia was positively associated with metabolites including acetylcarnosine (β = 0.34; 95% CI, 0.21-0.47; P = 1.27 × 10-6).In cohort study of patients with metastatic PDA, BMI was not associated with survival. Higher visceral fat density, subcutaneous fat area, and muscle-to-fascia ratio were associated with survival independent of BMI. The latter 2 were associated with higher levels of animal product metabolism. These findings could represent novel focuses for prognostication and intervention to improve survival of patients with PDA.