Abstract

Radiomics can quantify tumor phenotypic characteristics non-invasively by applying feature algorithms to medical imaging data. In this study of lung cancer patients, we investigated the association between radiomic features and the tumor histologic subtypes (adenocarcinoma and squamous cell carcinoma). Furthermore, in order to predict histologic subtypes, we employed machine-learning methods and independently evaluated their prediction performance. Two independent radiomic cohorts with a combined size of 350 patients were included in our analysis. A total of 440 radiomic features were extracted from the segmented tumor volumes of pretreatment CT images. These radiomic features quantify tumor phenotypic characteristics on medical images using tumor shape and size, intensity statistics, and texture. Univariate analysis was performed to assess each feature's association with the histological subtypes. In our multivariate analysis, we investigated 24 feature selection methods and 3 classification methods for histology prediction. Multivariate models were trained on the training cohort and their performance was evaluated on the independent validation cohort using the area under ROC curve (AUC). Histology was determined from surgical specimen. In our univariate analysis, we observed that fifty-three radiomic features were significantly associated with tumor histology. In multivariate analysis, feature selection methods ReliefF and its variants showed higher prediction accuracy as compared to other methods. We found that Naive Baye's classifier outperforms other classifiers and achieved the highest AUC (0.72; p-value = 2.3 × 10(-7)) with five features: Stats_min, Wavelet_HLL_rlgl_lowGrayLevelRunEmphasis, Wavelet_HHL_stats_median, Wavelet_HLL_stats_skewness, and Wavelet_HLH_glcm_clusShade. Histological subtypes can influence the choice of a treatment/therapy for lung cancer patients. We observed that radiomic features show significant association with the lung tumor histology. Moreover, radiomics-based multivariate classifiers were independently validated for the prediction of histological subtypes. Despite achieving lower than optimal prediction accuracy (AUC 0.72), our analysis highlights the impressive potential of non-invasive and cost-effective radiomics for precision medicine. Further research in this direction could lead us to optimal performance and therefore to clinical applicability, which could enhance the efficiency and efficacy of cancer care.

Highlights

  • Lung cancer is the leading cause of cancer-related deaths worldwide with 150,000 deaths per year in US [1]

  • Classification of the tumors as either adenocarcinoma or squamous cell carcinoma was based on hemotoxylin and eosin (H&E) staining according to the World Health Organization (WHO) classification of malignant lung tumors

  • A total of 440 radiomic features were investigated in terms of their association with and power to predict tumor histology

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Summary

Introduction

Lung cancer is the leading cause of cancer-related deaths worldwide with 150,000 deaths per year in US [1]. The most common histological subtypes of NSCLC are adenocarcinoma (~38%) and squamous cell carcinoma (~20%) [3]. Histological classification of lung cancer provides important information about tissue characteristics and anatomical location. Pemetrexed is the preferred treatment for stage IV lung adenocarcinoma, whereas bevacizumab is not recommended for squamous carcinoma due to the risk of pulmonary hemorrhage observed in phase II trials [8,9,10]. It has been shown that treatment for stage III lung cancer patients with squamous carcinoma has significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed, but for adenocarcinoma patients, the latter treatment provides superior survival rate [11, 12]. In this study of lung cancer patients, we investigated the association between radiomic features and the tumor histologic subtypes (adenocarcinoma and squamous cell carcinoma). In order to predict histologic subtypes, we employed machine-learning methods and independently evaluated their prediction performance

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