Abstract

Histopathological growth patterns (HGPs) are independent prognosticators for colorectal liver metastases (CRLM). Currently, HGPs are determined postoperatively. In this study, we evaluated radiomics for preoperative prediction of HGPs on computed tomography (CT), and its robustness to segmentation and acquisition variations. Patients with pure HGPs [i.e. 100% desmoplastic (dHGP) or 100% replacement (rHGP)] and a CT-scan who were surgically treated at the Erasmus MC between 2003–2015 were included retrospectively. Each lesion was segmented by three clinicians and a convolutional neural network (CNN). A prediction model was created using 564 radiomics features and a combination of machine learning approaches by training on the clinician’s and testing on the unseen CNN segmentations. The intra-class correlation coefficient (ICC) was used to select features robust to segmentation variations; ComBat was used to harmonize for acquisition variations. Evaluation was performed through a 100 × random-split cross-validation. The study included 93 CRLM in 76 patients (48% dHGP; 52% rHGP). Despite substantial differences between the segmentations of the three clinicians and the CNN, the radiomics model had a mean area under the curve of 0.69. ICC-based feature selection or ComBat yielded no improvement. Concluding, the combination of a CNN for segmentation and radiomics for classification has potential for automatically distinguishing dHGPs from rHGP, and is robust to segmentation and acquisition variations. Pending further optimization, including extension to mixed HGPs, our model may serve as a preoperative addition to postoperative HGP assessment, enabling further exploitation of HGPs as a biomarker.

Highlights

  • Colorectal liver metastases (CRLM) represent approximately 30% of all metastases in patients with colorectal carcinoma [1]

  • We focused on pure Histopathological growth patterns (HGPs) as these appear clinically more relevant than mixed HGPs, as a previous study showed that pure dHGP is an unmatched predictor for improved survival in chemo-naïve patients with CRLM [8]

  • The aim of this pilot was to evaluate whether radiomics can distinguish pure dHGPs from pure rHGPs based on computed tomography (CT)-scans and to evaluate its robustness to segmentation and acquisition protocol variations

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Summary

Introduction

Colorectal liver metastases (CRLM) represent approximately 30% of all metastases in patients with colorectal carcinoma [1]. Histopathological growth patterns (HGPs) have recently been identified as independent prognosticators in patients after CRLM resection [3]. The interface between tumor cells and normal liver parenchyma (NLP) is characterized by three distinct HGPs: two frequent (desmoplastic HGP (dHGP) and replacement HGP (rHGP), see Supplementary Fig. S1) and one rare (pushing HGP) type [4, 5]. A previous study found that dHGP patients have superior survival compared to mixed, replacement or pushing HGP patients [3]. Recent studies have suggested that HGPs could predict systemic chemotherapy effectiveness [6, 7]. More recent studies have shown that pure HGPs (i.e., 100% of the interface expresses the HGP) appear clinically more relevant [8]

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