Computer-assisted CRC lymph node metastases detection

Aim

Screening of lymph node metastases in colorectal cancer (CRC) can be a cumbersome task, but it is amenable to artificial intelligence (AI)-assisted diagnostic solutions. Here, we propose a deep learning–based workflow for the evaluation of CRC lymph node metastases from digitized hematoxylin and eosin–stained sections (Fig. 1). The proposed project has the following main objectives,

  1. To develop a lymph node metastasis detection workflow

  2. To validate the developed algorithms on a larger cohort from both internal and external centers

  3. To integrate the developed workflow into a stand-alone platform with overlaying results

Figure 1: A complete picture of this project is presented in the above workflow. A glass slide cohort of lymph node tissues can be digitized to Whole slide images by using in-house scanners. The deep learning algorithm can be trained for lymph node quantification with the help of pathologists’ experiences in terms of annotations. Upon detection of metastasis, the N-stage of a patient would be determined with the 2nd review of the experts.

Methods and results

As shown in Fig. 2, a segmentation model was trained on 100 whole-slide images (WSIs). It achieved a Matthews correlation coefficient of 0.86 (±0.154) and an acceptable Hausdorff distance of 135.59 μm (±72.14 μm), indicating a high congruence with the ground truth. For metastasis detection, 2 models (Xception and Vision Transformer) were independently trained first on a patch-based breast cancer lymph node data set and were then fine-tuned using the CRC data set. After fine-tuning, the ensemble model showed significant improvements in the F1 score (0.797-0.949; P <.00001) and the area under the receiver operating characteristic curve (0.959-0.978; P <.00001). Four independent cohorts (3 internal and 1 external) of CRC lymph nodes were used for validation in cascading segmentation and metastasis detection models. Our approach showed excellent performance, with high sensitivity (0.995, 1.0) and specificity (0.967, 1.0) in 2 validation cohorts of adenocarcinoma cases (n = 3836 slides) when comparing slide-level labels with the ground truth (pathologist reports). Similarly, an acceptable performance was achieved in a validation cohort (n = 172 slides) with mucinous and signet-ring cell histology (sensitivity, 0.872; specificity, 0.936). The patch-based classification confidence was aggregated to overlay the potential metastatic regions within each lymph node slide for visualization. We also applied our method to a consecutive case series of lymph nodes obtained over the past 6 months at our institution (n = 217 slides). The overlays of prediction within lymph node regions matched 100% when compared with a microscope evaluation by an expert pathologist (Fig. 3). Our results provide the basis for a computer-assisted diagnostic tool for easy and efficient lymph node screening in patients with CRC.

Figure 2: The deep learning workflow for colorectal cancer lymph node quantification consisting of 3 main tasks. In (A), the segmentation model (UNet) is trained for lymph node tissue segmentation. In (B), 2 neural network models, Xception and Vision Transformer (ViT16), are independently trained on PatchCamelyon (a publicly available breast cancer lymph node data set) for a positive and negative tissue classification task and are then fine-tuned on a CRC data set for a short cycle. Finally in (C), by cascading both segmentation (A) and metastasis detection models (B), validation is performed on large internal and external cohorts.

Figure 2: A few examples of whole slide images from subtypes of colorectal cancer adenocarcinomas with overlaying probability heatmaps of potential metastatic regions in lymph node tissues.

Members

Amjad Khan

Inti Zlobec

Jean-Philippe Thiran

Software and code

Github repository

Publications

Khan, A., Brouwer, N., Blank, A., Müller, F., Soldini, D., Noske, A., Gaus, E., Brandt, S., Nagtegaal, I., Dawson, H., Thiran, J.-P., Perren, A., Lugli, A., Zlobec, I. Computer-Assisted Diagnosis of Lymph Node Metastases in Colorectal Cancers Using Transfer Learning With an Ensemble Model. Modern Pathology, 2023, 36(5), 100118

Khan A, Janowczyk A, Müller F, Blank A, Nguyen HG, Abbet C, Studer L, Lugli A, Dawson H, Thiran JP, Zlobec I. Impact of scanner variability on lymph node segmentation in computational pathology. Journal of pathology informatics. 2022 1;13:100127