A radiomic signature model to predict the chemoradiation-induced alteration in tumor-infiltrating CD8⁺ cells in locally advanced rectal cancer

Background and purpose: Regarding the altered tumor immune status following cytotoxic treatment, this study aims to develop a radiomic signature to predict CD8⁺ tumor-infiltrating lymphocyte (TIL) density changes in chemoradiotherapy (CRT) of rectal cancer.

Materials and methods: We used the magnetic resonance imaging (MRI) and immunohistochemistry data before and after neoadjuvant CRT. The discovery datasets consisted of pre-CRT dataset A1 (n = 113), post-CRT datasets A2 (n = 32; predominance of tumor) and A3 (n = 20; pure fibrosis). The developed model was validated in dataset B (n = 28). Thirty-eight radiomic features from T2-weighted MRI scans were incorporated into the least absolute shrinkage and selection operator method.

Results: In pre-CRT dataset A1, the area under the receiver operating characteristic curve (AUC) values of radiomic score for predicting CD8⁺ TILs were 0.760 and 0.729 for training and validation subsets, respectively. A significant correlation was observed between the signature and CD8⁺ TIL density in the post-CRT dataset A2 (Pearson's R = -0.372, P = 0.036), whereas no association was found in dataset A3 (Pearson's R = -0.069, P = 0.77). The association was also observed in the validation dataset B (Pearson's R = -0.374, P = 0.049). In dataset A2, the radiomic score difference predicted changes in CD8⁺ TIL density (AUC = 0.824).

Conclusion: We established the MRI-derived radiomic signature for predicting CRT-induced alterations in CD8⁺ TILs. This study suggests the clinical utility of radiomics-immunophenotype modeling to evaluate tumor immune status following neoadjuvant chemoradiation in rectal cancer.