A multimodal synergistic model for personalized neoadjuvant immunochemotherapy in esophageal cancer

Cell Rep Med. 2025 Dec 16;6(12):102479. doi: 10.1016/j.xcrm.2025.102479. Epub 2025 Dec 8.

Abstract

Neoadjuvant immunochemotherapy (nICT) has significantly improved the treatment of locally advanced esophageal cancer (EC), yet accurately identifying patients' response remains a major challenge. In this study, we introduce eSPARK, a multimodal framework designed to integrate routinely available clinical data for informed decision-making in nICT treatment for EC. The model is developed using 344 patients from three independent regions, each with pre-treatment-paired computed tomography (CT) imaging and pathological slides, and postoperative pathological complete response (pCR) outcomes. By incorporating cytological semantic information, eSPARK demonstrates superior generalizability, outperforming single-modality models and achieving robust predictive accuracy across multicenter datasets. Additionally, a multi-scale interpretability module identifies several biomarkers, including the neutrophil-to-lymphocyte ratio (NLR) in the tumor microenvironment, associated with nICT response. Our findings underscore the potential of eSPARK as a powerful tool for personalized therapeutic decision-making in locally advanced EC and its broader implications for advancing precision oncology through multidisciplinary data integration.

Keywords: deep learning; esophageal cancer; multimodal; neoadjuvant immunochemotherapy.

MeSH terms

  • Aged
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / immunology
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / therapy
  • Female
  • Humans
  • Immunotherapy* / methods
  • Male
  • Middle Aged
  • Neoadjuvant Therapy* / methods
  • Neutrophils
  • Precision Medicine* / methods
  • Tumor Microenvironment