Introduction. This study compared the diagnostic test accuracy of magnetic resonance imaging (MRI) with that of 18 F-fluoro-2-glucose-positron emission tomography/ computed tomography (FDG-PET/CT) imaging in assessment of response to neoadjuvant chemotherapy (NAC) in breast cancer. Methods. A systematic search was performed in PubMed and EMBASE (last updated in June 2015). Studies investigating the performance of MRI and FDG-PET or FDG-PET/CT imaging during or after completion of NAC in patients with histologically proven breast cancer were eligible for inclusion. We considered only studies reporting a direct comparison between these imaging modalities to establish precise summary estimates in the same setting of patients. Pathologic response was considered as the reference standard. Two authors independently screened and selected studies that met the inclusion criteria and extracted the data.
Vascular endothelial cells (ECs) are responsible for post-ischemic angiogenesis, a process that is regulated by reactive oxygen species. Recent studies indicate that endothelial Nox4 based NADPH oxidase may have a key role. This study examines the role of endothelial Nox4 in ischemia-induced angiogenesis and explores the potential mechanisms involved. Mouse lines overexpressing human Nox4 wild type (EWT) or its dominant negative form P437H (EDN) specifically in the endothelium were used. Non-transgenic littermate mice (NTg) were used as controls. Following hind limb ischemia, blood flow recovery was enhanced in EWT and was impaired in EDN compared with NTg. The critical angiogenesis regulating genes vascular endothelial growth factor receptor2 (VEGFR2), endothelial nitric oxide synthase (eNOS) and transforming growth factor beta1 (TGFbeta1) were upregulated in EWT both in the ischemic muscle and in heart ECs, while TGFbeta1 was downregulated in EDNECs. In EC, both VEGFA and TGFbeta1 stimulated EC proliferation, migration, and capillary-like network formation in EWT but failed to do so in EDN. Application of TGFbeta1 increased both VEGFR2 and eNOS expression levels,whereas blocking TGFbeta1 or addition of catalase inhibited the phosphorylation of VEGFR2 and eNOS, indicating H2O2 and TGFbeta1 signaling downstream of Nox4 is critical to maintain EC angiogenic functions. Use of cell specific transgenic mice with both upregulation and downregulation of endothelial Nox4 indicate several mechanisms linked to Nox4 play a role in angiogenesis. Endothelial Nox4 regulates ischemia-induced angiogenesis, likely through H2O2- and TGFbeta1-mediated activation of cell signaling pathways essential for endothelial function.
Angiogenesis is a critical component of breast cancer development, and identification of imaging-based angiogenesis assays has prognostic and treatment implications. We evaluated the association of semi-quantitative kinetic and radiomic breast cancer features on dynamic contrast-enhanced (DCE)-MRI with microvessel density (MVD), a marker for angiogenesis. Invasive breast cancer kinetic features (initial peak percent enhancement [PE], signal enhancement ratio [SER], functional tumor volume [FTV], and washout fraction [WF]), radiomics features (108 total features reflecting tumor morphology, signal intensity, and texture), and MVD (by histologic CD31 immunostaining) were measured in 27 patients (1/2016–7/2017). Lesions with high MVD levels demonstrated higher peak SER than lesions with low MVD (mean: 1.94 vs. 1.61, area under the receiver operating characteristic curve [AUC] = 0.79, p = 0.009) and higher WF (mean: 50.6% vs. 22.5%, AUC = 0.87, p = 0.001). Several radiomics texture features were also promising for predicting increased MVD (maximum AUC = 0.84, p = 0.002). Our study suggests DCE-MRI can non-invasively assess breast cancer angiogenesis, which could stratify biology and optimize treatments.
Objectives
We aimed to determine the consistency of quantitative PET measurements of metabolic tumor volume (MTV) and intra-tumoral heterogeneity index for primary untreated pancreatic adenocarcinomas, when using dual-time-point 18F-FDG PET/CT imaging.
Methods
This is an Institutional Review Board approved, retrospective study including 71 patients with pancreatic adenocarcinoma, who underwent dual-time-point 18F-FDG PET/CT imaging, at ~1h (early) and ~2h (delayed), post injection. Automated gradient-based and 50% SUVmax-threshold segmentation methods were used to assess the primary tumor MTV, and metabolic intra-tumoral heterogeneity index, calculated as the area under Cumulative SUV-volume histograms (AUC-CSH), with lower AUC-CHS indexes corresponding to higher degrees of tumor heterogeneity. We defined that more than a ±10% change in MTV or AUC-CSH, compared to baseline, as clinically significant.
Results
71 FDG-avid pancreatic tumors were identified, with an average tumor diameter of 3.4±0.9 cm (range, 1.5 to 6.4 cm). MTV values remained consistent between early and delayed imaging when using the gradient PET segmentation method (p=0.086), whereas statistically significant change was seen when using 50% SUVmax-threshold segmentation (p <0.001). A decrease in more than 10% change in MTV (% ΔMTV) was observed in 70.4% (50/71) tumors, and 7.0% (5/71) of the tumors showed an increase more than 10 % ΔMTV, when using the 50% SUVmax-threshold segmentation. AUC-CSH indexes showed statistically significant differences between early and delayed time points (p<0.001), when using the gradient segmentation. AUC-CSH index decreased ≥10% in 40.8% (29/71) of the tumors. AUC-CSH index remained stable between early and delayed when using the 50% SUVmax-threshold segmentation (p=0.148) with % of change of less than 10% for all tumors.
Conclusion
Metabolic Tumor Volume was relatively stable between early and delayed time points when PET gradient segmentation was used but changed >10% in 77.4% of the tumors at delayed time point when threshold segmentation was used. The tumor heterogeneity index (AUC-CSH) changed >10% in 40.8% of tumors at delayed imaging, when gradient segmentation was used but remained stable when threshold segmentation was used. It is important to standardize uptake time and segmentation methods to use FDG PET metabolic tumor volume and heterogeneity index as imaging biomarkers.
Although incidental breast lesions were rarely detected on abdominal MRI, a considerable number of these lesions were found to represent breast cancer, particularly when leading to a recommendation for follow-up breast imaging. Therefore, it is important for radiologists interpreting abdominal MRI examinations to carefully evaluate for the presence of breast abnormalities.
The data in Tables E2, E3 (online) were incorrect and have been amended as follows: in Table E2 (online), .00 should be 0.98, 1.88 should be 1.87, 0.63 should be 0.62, and 0.60 should 0.59; in Table E3, 1.00 should be 0.97, 0.58 should be 0.57, −0.235 should be −0.24, and 1.84 should be 1.83
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.