Prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on MRI imaging using PDX

Jingzhen Shi; Jianbin Li; Zhenxiang Li; Yankang Li; Liang Xu; Yingjie Zhang

doi:10.3389/fonc.2023.1160815

Prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on MRI imaging using PDX

Front Oncol. 2023 Jun 12:13:1160815. doi: 10.3389/fonc.2023.1160815. eCollection 2023.

Authors

Jingzhen Shi^{1

2}, Jianbin Li³, Zhenxiang Li³, Yankang Li³, Liang Xu⁴, Yingjie Zhang³

Affiliations

¹ Department of Oncology, The Second Hospital of Tianjin Medical University, Tianjin, China.
² School of Medicine, Shandong University, Jinan, China.
³ Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
⁴ Department of Medical Imaging, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Abstract

Introduction: To confirm the efficacy of magnetic resonance-diffusion weighted imaging (MR-DWI) in esophageal squamous cell carcinoma (ESCC) early pathological response prediction and assessment to neoadjuvant chemoradiotherapy (nCRT) using patient-derived xenografts (PDXs).

Methods: PDX-bearing mice were randomly divided into two groups: the experimental group receiving cisplatin combined with radiotherapy, whereas the control group receiving normal saline. MRI scans were performed in treatment groups in the before, middle, and end of treatment. The correlations between tumor volumes, ADC values and tumor pathological response at different time nodes were explored. Then, expression of proliferation marker and apoptotic marker were detected using immunohistochemistry, and apoptosis rate was detected by TUNEL assay to further verify the results observed in the PDX models.

Results: The ADC values of the experimental group were significantly higher than the control group in the both middle and end stage of treatment (all P< 0.001), however, significant difference was only observed in tumor volume at the end stage of treatment (P< 0.001). Furthermore, the △ADC_mid-pre in our study may able to identify tumors with or without pCR to nCRT at an early stage, due to these changes were prior to the changes of tumor volume after treatment. Finally, TUNEL results also showed that the apoptosis rate of the experiment groups increased the most in the middle stage of treatment, especially the groups with pCR, but the highest apoptosis rate occurred in the end of the treatment. Further, the two PDX models with pCR exhibited the highest levels of apoptotic marker (Bax), and lowest levels of proliferation marker (PCNA and Ki-67) in the both middle and end stage of the treatment.

Conclusions: ADC values could be used to determine the tumor's response to nCRT, especially in the middle stages of treatment and before the tumor tissue morphology changes, and further, the ADC values were consistent with the potential biomarkers reflecting histopathological changes. Therefore, we suggest that radiation oncologists could refer to the ADC values in the middle stages of treatment when predicting the tumor histopathological response to n CRT in patients with ESCC.

Keywords: esophageal squamous cell carcinoma; magnetic resonance-diffusion weighted imaging; neoadjuvant chemoradiotherapy; pathological response grading; patient-derived xenograft.

Grants and funding

This study was supported by the National Natural Science Foundation of China (81773287); Taishan Schools Program of Shandong Province (NO.ts 20190982).