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.

BackgroundClinically, many esophageal cancer patients who planned for radiation therapy have already undergone diagnostic Positron-emission tomography/computed tomography (PET/CT) imaging, but it remains unclear whether these imaging results can be used to delineate the gross target volume (GTV) of the primary tumor for thoracic esophageal cancer (EC).MethodsSeventy-two patients diagnosed with thoracic EC had undergone prior PET/CT for diagnosis and three-dimensional CT (3DCT) for simulation. The GTV3D was contoured on the 3DCT image without referencing the PET/CT image. The GTVPET-ref was contoured on the 3DCT image referencing the PET/CT image. The GTVPET-reg was contoured on the deformed registration image derived from 3DCT and PET/CT. Differences in the position, volume, length, conformity index (CI), and degree of inclusion (DI) among the target volumes were determined.ResultsThe centroid distance in the three directions between two different GTVs showed no significant difference (P > 0.05). No significant difference was found among the groups in the tumor volume (P > 0.05). The median DI values of the GTVPET-reg and GTVPET-ref in the GTV3D were 0.82 and 0.86, respectively (P = 0.006). The median CI values of the GTV3D in the GTVPET-reg and GTVPET-ref were 0.68 and 0.72, respectively (P = 0.006).ConclusionsPET/CT can be used to optimize the definition of the target volume in EC. However, no significant difference was found between the GTVs delineated based on visual referencing or deformable registration whether using the volume or position. So, in the absence of planning PET–CT images, it is also feasible to delineate the GTV of primary thoracic EC with reference to the diagnostic PET–CT image.

Objective:To compare positional and volumetric differences between the gross target volumes (GTV) delineated on three-dimensional CT (3D-CT) referencing 18F-FDG PET/CT and the GTV on the deformed image derived from 3D-CT and 18F-FDG PET/CT for primary thoracic esophageal cancer (EC). Methods:Seventy-two patients underwent chemoradiotherapy were enrolled. All the patients sequentially underwent 18F-FDG PET/CT scans for diagnosis and 3D-CT scans for simulation. The GTV 3D was delineated on 3D-CT without referencing 18F-FDG PET/CT. The GTV PET-ref was delineated on 3D-CT referencing 18F-FDG PET/CT. The GTV PET-regwas delineated on the deformed image derived from 3D-CT and 18F-FDG PET/CT by MIM deformable registration software. The differences in position, volume, length, conformity index (CI), and degree of inclusion (DI) of target volumes were compared, respectively. Results:The median volume of GTV 3D, GTV PET-ref, GTV PET-reg were 44.90, 40.36 and 41.15 cm 3, respectively. There was no statistical difference between the volumes of any two targets. The mean lengths of GTV 3D, GTV PET-ref, GTV PET-reg were 8.54, 9.29 and 8.38 cm, respectively. The length of GTV PET-ref was longer than that of GTV 3D ( t=2.134, P<0.05). The median DIs of GTV PET-ref, GTV PET-regin GTV 3D were 0.86, 0.82( Z=-2.741, P<0.05), and that of GTV 3D in GTV PET-ref, GTV PET-reg were 0.87, 0.84 ( Z=-1.429, P<0.05). The median CIs of GTV 3D in GTV PET-ref and GTV PET-reg were 0.72, 0.68 ( Z=2.756, P<0.05), and the difference was significant. The CIs of GTV 3D and GTV PET-ref, GTV 3D and GTV PET-reg, GTV PET-ref and GTV PET-reg had significant negative correlation with the distance of target centers. Conclusions:There was no significant difference between GTV contoured on three-dimensional CT (3D-CT) referencing 18F-FDG PET/CT and the GTV on the deformed image derived from 3D-CT and 18F-FDG PET/CT either in volume size or in spatial position. Therefore, it is recommended that radiation oncologists can refer to the recent diagnostic PET/CT when delineating the gross target volume for primary thoracic esophageal cancer.

Objective:The aim of this study was to evaluate the safety and efficacy of anlotinib combined with chemoradiotherapy for treating esophageal squamous cell carcinoma (ESCC) using patient-derived xenografts (PDXs). Methods:PDX-bearing mice were randomly divided into five groups, as follows: control group receiving normal saline, the group receiving radiotherapy, the group receiving cisplatin combined with radiotherapy, the group receiving anlotinib combined with radiotherapy, and the group receiving anlotinib, and cisplatin combined with radiotherapy. Tumor volumes and body weights were measured three times weekly for 2 weeks. The PDXs were initially assessed by comparing the histology of the original patient tumor tissues with that of the corresponding serially passaged xenografts by hematoxylin and eosin (H&E) and P63 staining. Then, expression of Bax, c-PARP, PCNA, and CD31 was detected using immunohistochemistry, and apoptosis was detected by a TUNEL assay. Cytokines released into plasma were analyzed using protein chip technology. Finally, two case studies of ESCC patients were presented to further verify the results observed in the PDX models. Results:The pathological characteristics of the serially passaged patient tumor-derived xenografts established in our study were in line with those of the original ESCC patient samples. The group receiving anlotinib and cisplatin plus radiotherapy exhibited the strongest antitumor response among the groups. Moreover, the ideal anticancer effects of anlotinib combined with chemoradiotherapy observed in clinical patients were consistent with the results observed in the PDX models, and no serious side effects were observed during treatment. Conclusions:Combination therapy with anlotinib and chemoradiotherapy may be an effective regimen for the treatment of advanced ESCC.