Artificial intelligence for tumour tissue detection and histological regression grading in oesophageal adenocarcinomas: a retrospective algorithm development and validation study

Background: Oesophageal adenocarcinoma and adenocarcinoma of the oesophagogastric junction are among the most common malignant epithelial tumours. Most patients receive neoadjuvant therapy before complete tumour resection. Histological assessment after resection includes identification of residual tumour tissue and areas of regressive tumour, data which are used to calculate a clinically relevant regression score. We developed an artificial intelligence (AI) algorithm for tumour tissue detection and tumour regression grading in surgical specimens from patients with oesophageal adenocarcinoma or adenocarcinoma of the oesophagogastric junction.

Methods: We used one training cohort and four independent test cohorts to develop, train, and validate a deep learning tool. The material consisted of histological slides from surgically resected specimens from patients with oesophageal adenocarcinoma and adenocarcinoma of the oesophagogastric junction from three pathology institutes (two in Germany, one in Austria) and oesophageal cancer cohort of The Cancer Genome Atlas (TCGA). All slides were from neoadjuvantly treated patients except for those from the TCGA cohort, who were neoadjuvant-therapy naive. Data from training cohort and test cohort cases were extensively manually annotated for 11 tissue classes. A convolutional neural network was trained on the data using a supervised principle. First, the tool was formally validated using manually annotated test datasets. Next, tumour regression grading was assessed in a retrospective cohort of post-neoadjuvant therapy surgical specimens. The grading of the algorithm was compared with that of a group of 12 board-certified pathologists from one department. To further validate the tool, three pathologists processed whole resection cases with and without AI assistance.

Findings: Of the four test cohorts, one included 22 manually annotated histological slides (n=20 patients), one included 62 sides (n=15), one included 214 slides (n=69), and the final one included 22 manually annotated histological slides (n=22). In the independent test cohorts the AI tool had high patch-level accuracy for identifying both tumour and regression tissue. When we validated the concordance of the AI tool against analyses by a group of pathologists (n=12), agreement was 63·6% (quadratic kappa 0·749; p<0·0001) at case level. The AI-based regression grading triggered true reclassification of resected tumour slides in seven cases (including six cases who had small tumour regions that were initially missed by pathologists). Use of the AI tool by three pathologists increased interobserver agreement and substantially reduced diagnostic time per case compared with working without AI assistance.

Interpretation: Use of our AI tool in the diagnostics of oesophageal adenocarcinoma resection specimens by pathologists increased diagnostic accuracy, interobserver concordance, and significantly reduced assessment time. Prospective validation of the tool is required.

Funding: North Rhine-Westphalia state, Federal Ministry of Education and Research of Germany, and the Wilhelm Sander Foundation.