Abstract

Background:Cancer typically exhibits genotypic and phenotypic heterogeneity, which can have prognostic significance and influence therapy response. Computed Tomography (CT)-based radiomic approaches calculate quantitative features of tumour heterogeneity at a mesoscopic level, regardless of macroscopic areas of hypo-dense (i.e., cystic/necrotic), hyper-dense (i.e., calcified), or intermediately dense (i.e., soft tissue) portions. Method:With the goal of achieving the automated sub-segmentation of these three tissue types, we present here a two-stage computational framework based on unsupervised Fuzzy C-Means Clustering (FCM) techniques. No existing approach has specifically addressed this task so far. Our tissue-specific image sub-segmentation was tested on ovarian cancer (pelvic/ovarian and omental disease) and renal cell carcinoma CT datasets using both overlap-based and distance-based metrics for evaluation. Results:On all tested sub-segmentation tasks, our two-stage segmentation approach outperformed conventional segmentation techniques: fixed multi-thresholding, the Otsu method, and automatic cluster number selection heuristics for the K-means clustering algorithm. In addition, experiments showed that the integration of the spatial information into the FCM algorithm generally achieves more accurate segmentation results, whilst the kernelised FCM versions are not beneficial. The best spatial FCM configuration achieved average Dice similarity coefficient values starting from 81.94±4.76 and 83.43±3.81 for hyper-dense and hypo-dense components, respectively, for the investigated sub-segmentation tasks. Conclusions:The proposed intelligent framework could be readily integrated into clinical research environments and provides robust tools for future radiomic biomarker validation.

Highlights

  • Cancer is typically characterised by genotypic and phenotypic heterogeneity, which has prognostic significance and may influence the response to therapy [1]

  • SFCM V)&01V,)2&0 V)&0 Gol*dROGs6tWaDQnGDdUGard dense and hypo-dense tissue segmentation are depicted in Figs. 7a and 7b, respectively

  • The delineations of all the kernelised sFCM (ksFCM) are less accurate than those achieved by sFCM1,2

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Summary

Introduction

Cancer is typically characterised by genotypic and phenotypic heterogeneity, which has prognostic significance and may influence the response to therapy [1]. Intra- and inter-tumoural heterogeneity can be quantified on the mesoscopic level by using CT-based radiomics, which has been 10 shown to hold both predictive and prognostic information for many cancer types, including high-grade serous ovarian carcinoma (HGSOC) and renal cell carcinoma (RCC). These two cancer types are characterised by high levels of macroscopic heterogeneity with frequent cystic/necrotic, solid, and calcified tumour regions [3,4,5,6,7,8,9].

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