Leijenaar Ralph Th, Bogowicz Marta, Jochems Arthur, Hoebers Frank Jp, Wesseling Frederik Wr, Huang Sophie H, Chan Biu, Waldron John N, O'Sullivan Brian, Rietveld Derek, Leemans C Rene, Brakenhoff Ruud H, Riesterer Oliver, Tanadini-Lang Stephanie, Guckenberger Matthias, Ikenberg Kristian, Lambin Philippe
1 The D-Lab: Decision Support for Precision Medicine GROW - School for Oncology and Developmental Biology & MCCC Maastricht University Medical Centre+ Maastricht , Maastricht , Netherlands.
2 Department of Radiation Oncology, University Hospital Zurich and University of Zurich , Zurich , Switzerland.
Br J Radiol. 2018 Jun;91(1086):20170498. doi: 10.1259/bjr.20170498. Epub 2018 Mar 22.
Human papillomavirus (HPV) positive oropharyngeal cancer (oropharyngeal squamous cell carcinoma, OPSCC) is biologically and clinically different from HPV negative OPSCC. Here, we evaluate the use of a radiomic approach to identify the HPV status of OPSCC.
Four independent cohorts, totaling 778 OPSCC patients with HPV determined by p16 were collected. We randomly assigned 80% of all data for model training (N = 628) and 20% for validation (N = 150). On the pre-treatment CT images, 902 radiomic features were calculated from the gross tumor volume. Multivariable modeling was performed using least absolute shrinkage and selection operator. To assess the impact of CT artifacts in predicting HPV (p16), a model was developed on all training data (M) and on the artifact-free subset of training data (M). Models were validated on all validation data (V), and the subgroups with (V) and without (V) artifacts. Kaplan-Meier survival analysis was performed to compare HPV status based on p16 and radiomic model predictions.
The area under the receiver operator curve for M and M ranged between 0.70 and 0.80 and was not significantly different for all validation data sets. There was a consistent and significant split between survival curves with HPV status determined by p16 [p = 0.007; hazard ratio (HR): 0.46], M (p = 0.036; HR: 0.55) and M (p = 0.027; HR: 0.49).
This study provides proof of concept that molecular information can be derived from standard medical images and shows potential for radiomics as imaging biomarker of HPV status. Advances in knowledge: Radiomics has the potential to identify clinically relevant molecular phenotypes.
人乳头瘤病毒(HPV)阳性口咽癌(口咽鳞状细胞癌,OPSCC)在生物学和临床上与HPV阴性OPSCC不同。在此,我们评估使用放射组学方法来识别OPSCC的HPV状态。
收集了四个独立队列,共778例经p16确定HPV状态的OPSCC患者。我们将所有数据的80%随机分配用于模型训练(N = 628),20%用于验证(N = 150)。在治疗前的CT图像上,从大体肿瘤体积计算出902个放射组学特征。使用最小绝对收缩和选择算子进行多变量建模。为了评估CT伪影对预测HPV(p16)的影响,在所有训练数据(M)和训练数据的无伪影子集中开发了一个模型。在所有验证数据(V)以及有(V)和无(V)伪影的亚组上对模型进行验证。进行Kaplan-Meier生存分析以比较基于p16和放射组学模型预测的HPV状态。
M和M的受试者操作特征曲线下面积在0.70至0.80之间,并且在所有验证数据集中无显著差异。由p16确定的HPV状态的生存曲线之间存在一致且显著的差异[p = 0.007;风险比(HR):0.46],M(p = 0.036;HR:0.55)和M(p = 0.027;HR:0.49)。
本研究提供了概念验证,即分子信息可从标准医学图像中得出,并显示了放射组学作为HPV状态成像生物标志物的潜力。知识进展:放射组学有潜力识别临床相关的分子表型。