Deep learning-based prediction of HER2 status and trastuzumab treatment efficacy of gastric adenocarcinoma based on morphological features.

Background: First-line treatment for advanced gastric adenocarcinoma (GAC) with human epidermal growth factor receptor 2 (HER2) is trastuzumab combined with chemotherapy. In clinical practice, HER2 positivity is identified through immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), whereas deep learning (DL) can predict HER2 status based on tumor histopathological features. However, it remains uncertain whether these deep learning-derived features can predict the efficacy of anti-HER2 therapy.

Methods: We analyzed a cohort of 300 consecutive surgical specimens and 101 biopsy specimens, all undergoing HER2 testing, along with 41 biopsy specimens receiving trastuzumab-based therapy for HER2-positive GAC.

Results: We developed a convolutional neural network (CNN) model using surgical specimens that achieved an area under the curve (AUC) value of 0.847 in predicting HER2 amplification, and achieved an AUC of 0.903 in predicting HER2 status specifically in patients with HER2 2 + expression. The model also predicted HER2 status in gastric biopsy specimens, achieving an AUC of 0.723. Furthermore, our classifier was trained using 41 HER2-positive gastric biopsy specimens that had undergone trastuzumab treatment, our model demonstrated an AUC of 0.833 for the (CR + PR) / (SD + PD) subgroup.

Conclusion: This work explores an algorithm that utilizes hematoxylin and eosin (H&E) staining to accurately predict HER2 status and assess the response to trastuzumab in GAC, potentially facilitating clinical decision-making.