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

IntroductionTo 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)MethodsPDX-bearing mice were...

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Main Authors: Jingzhen Shi, Jianbin Li, Zhenxiang Li, Yankang Li, Liang Xu, Yingjie Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1160815/full
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author Jingzhen Shi
Jingzhen Shi
Jianbin Li
Zhenxiang Li
Yankang Li
Liang Xu
Yingjie Zhang
author_facet Jingzhen Shi
Jingzhen Shi
Jianbin Li
Zhenxiang Li
Yankang Li
Liang Xu
Yingjie Zhang
author_sort Jingzhen Shi
collection DOAJ
description IntroductionTo 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)MethodsPDX-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.ResultsThe 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 △ADCmid-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.ConclusionsADC 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.
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spelling doaj.art-7208bc0df6ba4e3090001d273d43c8be2023-06-12T09:15:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-06-011310.3389/fonc.2023.11608151160815Prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on MRI imaging using PDXJingzhen Shi0Jingzhen Shi1Jianbin Li2Zhenxiang Li3Yankang Li4Liang Xu5Yingjie Zhang6Department of Oncology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaSchool of Medicine, Shandong University, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Medical Imaging, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaIntroductionTo 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)MethodsPDX-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.ResultsThe 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 △ADCmid-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.ConclusionsADC 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.https://www.frontiersin.org/articles/10.3389/fonc.2023.1160815/fullpatient-derived xenograftesophageal squamous cell carcinomamagnetic resonance-diffusion weighted imagingpathological response gradingneoadjuvant chemoradiotherapy
spellingShingle Jingzhen Shi
Jingzhen Shi
Jianbin Li
Zhenxiang Li
Yankang Li
Liang Xu
Yingjie Zhang
Prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on MRI imaging using PDX
Frontiers in Oncology
patient-derived xenograft
esophageal squamous cell carcinoma
magnetic resonance-diffusion weighted imaging
pathological response grading
neoadjuvant chemoradiotherapy
title Prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on MRI imaging using PDX
title_full Prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on MRI imaging using PDX
title_fullStr Prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on MRI imaging using PDX
title_full_unstemmed Prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on MRI imaging using PDX
title_short Prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on MRI imaging using PDX
title_sort prediction of pathological response grading for esophageal squamous carcinoma after neoadjuvant chemoradiotherapy based on mri imaging using pdx
topic patient-derived xenograft
esophageal squamous cell carcinoma
magnetic resonance-diffusion weighted imaging
pathological response grading
neoadjuvant chemoradiotherapy
url https://www.frontiersin.org/articles/10.3389/fonc.2023.1160815/full
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