Joint Department of Medical Imaging, University Health Network, Sinai Health System and Women's College Hospital, University of Toronto, Toronto, ON, Canada.
Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
Eur Radiol. 2022 Apr;32(4):2492-2505. doi: 10.1007/s00330-021-08314-w. Epub 2021 Nov 10.
In resectable pancreatic ductal adenocarcinoma (PDAC), few pre-operative prognostic biomarkers are available. Radiomics has demonstrated potential but lacks external validation. We aimed to develop and externally validate a pre-operative clinical-radiomic prognostic model.
Retrospective international, multi-center study in resectable PDAC. The training cohort included 352 patients (pre-operative CTs from five Canadian hospitals). Cox models incorporated (a) pre-operative clinical variables (clinical), (b) clinical plus CT-radiomics, and (c) post-operative TNM model, which served as the reference. Outcomes were overall (OS)/disease-free survival (DFS). Models were assessed in the validation cohort from Ireland (n = 215, CTs from 34 hospitals), using C-statistic, calibration, and decision curve analyses.
The radiomic signature was predictive of OS/DFS in the validation cohort, with adjusted hazard ratios (HR) 2.87 (95% CI: 1.40-5.87, p < 0.001)/5.28 (95% CI 2.35-11.86, p < 0.001), respectively, along with age 1.02 (1.01-1.04, p = 0.01)/1.02 (1.00-1.04, p = 0.03). In the validation cohort, median OS was 22.9/37 months (p = 0.0092) and DFS 14.2/29.8 (p = 0.0023) for high-/low-risk groups and calibration was moderate (mean absolute errors 7%/13% for OS at 3/5 years). The clinical-radiomic model discrimination (C = 0.545, 95%: 0.543-0.546) was higher than the clinical model alone (C = 0.497, 95% CI 0.496-0.499, p < 0.001) or TNM (C = 0.525, 95% CI: 0.524-0.526, p < 0.001). Despite superior net benefit compared to the clinical model, the clinical-radiomic model was not clinically useful for most threshold probabilities.
A multi-institutional pre-operative clinical-radiomic model for resectable PDAC prognostication demonstrated superior net benefit compared to a clinical model but limited clinical utility at external validation. This reflects inherent limitations of radiomics for PDAC prognostication, when deployed in real-world settings.
• At external validation, a pre-operative clinical-radiomics prognostic model for pancreatic ductal adenocarcinoma (PDAC) outperformed pre-operative clinical variables alone or pathological TNM staging. • Discrimination and clinical utility of the clinical-radiomic model for treatment decisions remained low, likely due to heterogeneity of CT acquisition parameters. • Despite small improvements, prognosis in PDAC using state-of-the-art radiomics methodology remains challenging, mostly owing to its low discriminative ability. Future research should focus on standardization of CT protocols and acquisition parameters.
在可切除的胰腺导管腺癌（PDAC）中，可用的术前预后生物标志物很少。放射组学已显示出一定的潜力，但缺乏外部验证。我们旨在开发和外部验证一种术前临床放射组学预后模型。
这是一项可切除 PDAC 的回顾性国际多中心研究。训练队列包括 352 名患者（来自加拿大五家医院的术前 CT）。Cox 模型纳入了（a）术前临床变量（临床），（b）临床加 CT-放射组学，以及（c）术后 TNM 模型，后者作为参考。结局是总生存（OS）/无病生存（DFS）。在爱尔兰的验证队列（n=215，来自 34 家医院的 CT）中，使用 C 统计量、校准和决策曲线分析评估模型。
在验证队列中，放射组学特征可预测 OS/DFS，调整后的风险比（HR）分别为 2.87（95%CI：1.40-5.87，p<0.001）/5.28（95%CI 2.35-11.86，p<0.001），以及年龄 1.02（1.01-1.04，p=0.01）/1.02（1.00-1.04，p=0.03）。在验证队列中，高风险/低风险组的中位 OS 分别为 22.9/37 个月（p=0.0092）和 DFS 分别为 14.2/29.8 个月（p=0.0023），校准结果为中度（OS 3/5 年的平均绝对误差分别为 7%/13%）。临床放射组学模型的区分度（C=0.545，95%：0.543-0.546）高于临床模型单独（C=0.497，95%CI 0.496-0.499，p<0.001）或 TNM（C=0.525，95%CI：0.524-0.526，p<0.001）。尽管与临床模型相比，多机构术前临床放射组学模型在预测可切除 PDAC 预后方面具有更高的净获益，但在外部验证时，其临床实用性有限。这反映了放射组学在实际情况下对 PDAC 预后的固有局限性。
• 在外部验证中，术前临床放射组学 PDAC 预后模型在预测方面优于术前临床变量单独或病理 TNM 分期。• 临床放射组学模型用于治疗决策的区分度和临床实用性仍然较低，这可能是由于 CT 采集参数的异质性所致。• 尽管有微小的改善，但使用最先进的放射组学方法预测 PDAC 的预后仍然具有挑战性，主要是由于其低区分能力。未来的研究应集中在 CT 协议和采集参数的标准化上。
