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Abstract
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.

Affiliations

Seung Hyuck Jeon 1, Yu Jin Lim 2, Jaemoon Koh 3, Won Ick Chang 4, Sehui Kim 3, Kyubo Kim 5, Eui Kyu Chie 6
1Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
2Department of Radiation Oncology, Kyung Hee University College of Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea.
3Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
4Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.
5Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, Republic of Korea.
6Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea. Electronic address: ekchie93@snu.ac.kr.