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Relationship between Tumor volume and MR parameters in advanced stages of PDAC. (A) showing relationship between Tumor volume and T1 (ms); (B) showing relationship between Tumor Volume and T2 (ms); (C) showing relationship between Tumor volume and MTR (%).
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Simple Summary
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a poor prognosis. A better understanding of the tumor microenvironment may help better treat the disease. Magnetic resonance imaging may be a great tool for monitoring the tumor microenvironment at different stages of tumor evolution. Here, we used multi-parametric magn...
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Citations
... In our study, the NIC of PVP in the Ki-67 high expression set was significantly lower than that in the Ki-67 low expression set in the training cohort (0.33 vs. 0.24, p < 0.001). The possible reasons for this were the fact that high Ki-67 expression represents active cell proliferation, whereas ischaemia and hypoxia due to active cell proliferation in PDAC constitute the microenvironment for the growth of PDAC and that PDAC is a less vascular tumour with a high fibrous stromal component [27]. The ECVf is a quantitative indicator of the extravascular space and extracellular space, and the extravascular space and extracellular space are important parts of the cellular microenvironment. ...
Objective
To construct and validate a model based on the dual-energy computed tomography (DECT) quantitative parameters and radiological features to predict Ki-67 expression levels in pancreatic ductal adenocarcinoma (PDAC).
Materials and methods
Data from 143 PDAC patients were analysed. The variables of clinic, radiology and DECT were evaluated. In the arterial phase and portal venous phase (PVP), the normalized iodine concentration (NIC), normalized effective atomic number and slope of the spectral attenuation curves were measured. The extracellular volume fraction (ECVf) was measured in the equilibrium phase. Univariate analysis was used to screen independent risk factors to predict Ki-67 expression. The Radiology, DECT and DECT–Radiology models were constructed, and their diagnostic effectiveness and clinical applicability were obtained through area under the curve (AUC) and decision curve analysis, respectively. The nomogram was established based on the optimal model, and its goodness-of-fit was assessed by a calibration curve.
Results
Computed tomography reported regional lymph node status, NIC of PVP, and ECVf were independent predictors for Ki-67 expression prediction. The AUCs of the Radiology, DECT, and DECT–Radiology models were 0.705, 0.884, and 0.905, respectively, in the training cohort, and 0.669, 0.835, and 0.865, respectively, in the validation cohort. The DECT–Radiology nomogram was established based on the DECT–Radiology model, which showed the highest net benefit and satisfactory consistency.
Conclusions
The DECT–Radiology model shows favourable predictive efficacy for Ki-67 expression, which may be of value for clinical decision-making in PDAC patients.
Critical relevance statement
The DECT–Radiology model could contribute to the preoperative and non-invasive assessment of Ki-67 expression of PDAC, which may help clinicians to screen out PDAC patients with high Ki-67 expression.
Key points
• Dual-energy computed tomography (DECT) can predict Ki-67 in pancreatic ductal adenocarcinoma (PDAC).
• The DECT–Radiology model facilitates preoperative and non-invasive assessment of PDAC Ki-67 expression.
• The nomogram may help screen out PDAC patients with high Ki-67 expression.
Graphical Abstract
Pulsed high intensity focused ultrasound (pHIFU) is a non-invasive method that allows to permeabilize pancreatic tumors through inertial cavitation and thereby increase the concentration of systemically administered drug. In this study the tolerability of weekly pHIFU-aided administrations of gemcitabine (gem) and their influence on tumor progression and immune microenvironment were investigated in genetically engineered KrasLSL.G12D/þ; p53R172H/þ; PdxCretg/þ (KPC) mouse model of spontaneously occurring pancreatic tumors. KPC mice were enrolled in the study when the tumor size reached 4-6 mm and treated once a week with either ultrasound-guided pHIFU (1.5 MHz transducer, 1 ms pulses, 1% duty cycle, peak negative pressure 16.5 MPa) followed by administration of gem (n = 9), gem only (n = 5) or no treatment (n = 8). Tumor progression was followed by ultrasound imaging until the study endpoint (tumor size reaching 1 cm), whereupon the excised tumors were analyzed by histology, immunohistochemistry (IHC) and gene expression profiling (Nanostring PanCancer Immune Profiling panel). The pHIFU + gem treatments were well tolerated; the pHIFU-treated region of the tumor turned hypoechoic immediately following treatment in all mice, and this effect persisted throughout the observation period (2-5 weeks) and corresponded to areas of cell death, according to histology and IHC. Enhanced labeling by Granzyme-B was observed within and adjacent to the pHIFU treated area, but not in the non-treated tumor tissue; no difference in CD8 + staining was observed between the treatment groups. Gene expression analysis showed that the pHIFU + gem combination treatment lead to significant downregulation of 162 genes related to immunosuppression, tumorigenesis, and chemoresistance vs gem only treatment.
Pancreatic cancer is one of the most lethal malignancies in the world. Cancer-associated fibroblasts are one of the main components of tumor microenvironment in pancreatic cancer and play an essential role in tumor progression. Fibroblast activation protein that is expressed in specific subtypes of cancer-associated fibroblasts promotes tumor growth and is related to poor survival. Recent researches have preliminarily demonstrated a promising potential of radiopharmaceuticals targeting fibroblast activation protein in diagnosis and therapy of pancreatic cancer. This article comprehensively reviews the current development and clinical translation of fibroblast activation protein inhibitor-targeting radiopharmaceuticals in pancreatic cancer and provides significant perspectives for future investigations.
