Preoperative CT-based radiomics combined with intraoperative frozen section is predictive of invasive adenocarcinoma in pulmonary nodules: a multicenter study
术前基于 CT 的影像组学联合术中冰冻切片预测肺结节浸润性腺癌的多中心研究
- 作者列表："Wu, Guangyao","Woodruff, Henry C.","Sanduleanu, Sebastian","Refaee, Turkey","Jochems, Arthur","Leijenaar, Ralph","Gietema, Hester","Shen, Jing","Wang, Rui","Xiong, Jingtong","Bian, Jie","Wu, Jianlin","Lambin, Philippe
Objectives Develop a CT-based radiomics model and combine it with frozen section (FS) and clinical data to distinguish invasive adenocarcinomas (IA) from preinvasive lesions/minimally invasive adenocarcinomas (PM). Methods This multicenter study cohort of 623 lung adenocarcinomas was split into training ( n = 331), testing ( n = 143), and external validation dataset ( n = 149). Random forest models were built using selected radiomics features, results from FS, lesion volume, clinical and semantic features, and combinations thereof. The area under the receiver operator characteristic curves (AUC) was used to evaluate model performances. The diagnosis accuracy, calibration, and decision curves of models were tested. Results The radiomics-based model shows good predictive performance and diagnostic accuracy for distinguishing IA from PM, with AUCs of 0.89, 0.89, and 0.88, in the training, testing, and validation datasets, respectively, and with corresponding accuracies of 0.82, 0.79, and 0.85. Adding lesion volume and FS significantly increases the performance of the model with AUCs of 0.96, 0.97, and 0.96, and with accuracies of 0.91, 0.94, and 0.93 in the three datasets. There is no significant difference in AUC between the FS model enriched with radiomics and volume against an FS model enriched with volume alone, while the former has higher accuracy. The model combining all available information shows minor non-significant improvements in AUC and accuracy compared with an FS model enriched with radiomics and volume. Conclusions Radiomics signatures are potential biomarkers for the risk of IA, especially in combination with FS, and could help guide surgical strategy for pulmonary nodules patients. Key Points • A CT-based radiomics model may be a valuable tool for preoperative prediction of invasive adenocarcinoma for patients with pulmonary nodules. • Radiomics combined with frozen sections could help in guiding surgery strategy for patients with pulmonary nodules.
目的建立基于 CT 的影像组学模型，并将其与冰冻切片 (FS) 和临床数据相结合，以区分侵袭性腺癌 (IA) 和侵袭前病变/微创腺癌 (PM)。方法将 623 例肺腺癌的多中心研究队列分为培训 (n = 331) 、测试 (n = 143) 、和外部验证数据集 (n = 149)。使用选定的放射组学特征、 FS 结果、病变体积、临床和语义特征及其组合构建随机森林模型。受试者操作者特征曲线下面积 (AUC) 用于评价模型性能。测试模型的诊断准确性、校准和决策曲线。结果基于 radiomics 的模型在区分 IA 和 PM 方面显示了良好的预测性能和诊断准确性，在训练、测试和验证数据集中的 auc 为 0.89 、 0.89 和 0.88, 分别和相应的精度为 0.82，0.79 和 0.85。增加病变体积和 FS 显著提高了模型的性能，auc 为 0.96 、 0.97 和 0.96，在三个数据集中的准确性为 0.91 、 0.94 和 0.93。富集 radiomics 和 volume 的 FS 模型与单独富集 volume 的 FS 模型的 AUC 无显著差异，而前者具有更高的准确性。结合所有可用信息的模型显示，与富含放射组学和体积的 FS 模型相比，AUC 和准确性有轻微的非显著改善。结论放射组学标记是 IA 风险的潜在生物标志物，尤其是与 FS 联合应用，有助于指导肺结节患者的手术策略。要点 • 基于 CT 的影像组学模型可能是术前预测肺结节患者浸润性腺癌的有价值的工具。•放射组学联合冰冻切片可帮助指导肺结节患者的手术策略。
METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.
METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.
METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.