Artificial intelligence-assisted analysis for tumor-immune interaction within the invasive margin of colorectal cancer

BACKGROUND: In colorectal cancer (CRC), both tumor invasion and immunological analysis at the tumor invasive margin (IM) are significantly associated with patient prognosis, but have traditionally been reported independently. We propose a new scoring system, the TGP-I score, to assess the association and interactions between tumor growth pattern (TGP) and tumor infiltrating lymphocytes at the IM and to predict its prognostic validity for CRC patient stratification. MATERIALS AND METHODS: The types of TGP were assessed in hematoxylin and eosin-stained whole-slide images. The CD3(+) T-cells density at the IM was automatically quantified on immunohistochemical-stained slides using a deep learning method. A discovery (N = 347) and a validation (N = 132) cohorts were used to evaluate the prognostic value of the TGP-I score for overall survival. RESULTS: The TGP-I score(3) (trichotomy) was an independent prognostic factor, with higher TGP-I score(3) associated with worse prognosis in the discovery (unadjusted hazard ratio [HR] for high vs. low 3.62, 95% confidence interval [CI] 2.22–5.90; p < 0.001) and validation cohort (unadjusted HR for high vs. low 5.79, 95% CI 1.84–18.20; p = 0.003). The relative contribution of each parameter to predicting survival was analyzed. The TGP-I score(3) had similar importance compared to tumor-node-metastasis staging (31.2% vs. 32.9%) and was stronger than other clinical parameters. CONCLUSIONS: This automated workflow and the proposed TGP-I score could further provide accurate prognostic stratification and have potential value for supporting the clinical decision-making of stage I–III CRC patients. KEY MESSAGES: A new scoring system, the TGP-I score, was proposed to assess the association and interactions of TGP and TILs at the tumor invasive margin. TGP-I score could be an independent predictor of prognosis for CRC patients, with higher scores being associated with worse survival. TGP-I score had similar importance compared to tumor-node-metastasis staging and was stronger than other clinical parameters.