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  • It is noteworthy that even with low tumor burden

    2019-06-12

    It is noteworthy that, even with low tumor burden in these patients following CR, peak value at CR status is still a useful indicator for OS, both in the whole cohort, and more importantly, in the intermediate-risk subgroup. Slope is mainly determined by tissue vascularization and perfusion, but capillary permeability may also play an important role. A previous study showed that high values for amplitude at initial DCE MRI is a poor risk factor for disease-free and overall survival in AML patients. In addition, a high value for amplitude at DCE MRI in patients in CR is also associated with shorter OS. Kep, a rate transfer coefficient, represents contrast exchange between blood plasma and extravascular extracellular space. It was strongly influenced by permeability and also positively correlated with the perfusion and plasma volume but negatively associated with the interstitial volume. According to the hypothesis, antiangiogenic agents can normalize abnormal tumor vasculature, resulting in more efficient delivery of drugs and oxygen to targeted cancer cells. Under this assumption, when patients achieve CR, bone marrow vessels and their endothelium should be normalized with reduced vessel wall permeability, and bone marrow cells should return to normal karyotype. Failure of this repair process would result in persistent high vascular permeability and a high value for Kep. Therefore, increased values for Kep in patients with CR status who undergo DCE MR imaging may indicate a high risk of relapse and shorter OS and RFS. The high permeability of the bone marrow may also be associated with high vascular endothelial growth factor protein expression. A high level of vascular endothelial growth factor expression in tumor cells is associated with neovascularization, tumor aggressiveness, and poor prognosis in AML patients. The result implies that Kep at remission status, representing the interaction of capillary endothelial permeability, interstitial or intraosseous pressure, and diffusion of molecules between the Talabostat mesylate and the interstitial space, may be a suitable marker for current angiogenesis. In multiple myeloma (MM) patients, the angiogenesis parameters generated from DCE-MRI of vertebral BM reportedly also correlate strongly with histological grade of infiltration, osteolytic bone involvement, microvessel density (MVD), and serum markers of disease activity. Extramedullary Disease (EMD) in patients with MM was defined as the presence of MCs outside BM, in one of the following forms: soft-tissue mass spreading from the bone (periosseous plasmacytoma), MCs arising in extraosseous organs (extraosseous plasmacytoma), malignant effusion, or plasma cell leukemia. The presence of EMD was diagnosed in most cases by MRI or computed tomography, which were conducted whenever EMD was suspected from clinical, laboratory, or radiographic findings. However, no data of prior study were available on the correlation between degree of BM angiogenesis and the development of EMD in MM patients. Huang et al. examined the correlation between angiogenesis parameters generated from DCE-MRI of vertebral bodies, together with MVD in BM (obtained from the posterior iliac crest), with the manifestation of EMD in patients with MM. The mean MVD with significant differences being found for patients in different subgroups. Patients with extramedullary disease (EMD) had a higher mean MVD of 20.3 (95% confidence interval [CI: 15.3–25.2]), patients in the non-EMD group had a lower mean MVD of 3.2 (95% CI: 1.4–5.0); but patients with progression disease had a mean MVD of 15.7 (95% CI: 9.9–21.5). The time–signal intensity (SI) curve shown in DCE-MRI correlated strongly with tissue MVD, where a high peak and steep slope were associated with high MVD. By contrast, a lower peak and gentler slope were associated with lower MVD. Moderate correlations were found between MVD and the two semi-quantitative parameters Peak and Slope (both p < 0.001). The quantitative parameters, Amp and Kel, but not Kep, were also moderately correlated with MVD. Other salient characteristics significantly correlated with MVD were beta2-microglobulin, C-reactive protein, and percentage of MCs in BM. Further multiple linear regression analysis showed that only Amp and percentage of MCs in BM were independently correlated with MVD. In addition, multiple logistic regression model showed that Amp was the only significant factor associated with EMD (OR = 6.33). The accumulative incidence for development of EMD over time was significantly higher for patients with high Amp (>0.08) than for patients with low Amp (<0.08). Additional covariates were identified by univariate analysis as being significantly associated with the development of EMD, including light chain isotype, high Kel (>0.10), and high calcium (>2.4 mmol/l). However, multivariate analysis using the Cox regression model did not confirm that any of these factors was independently significant. This study demonstrates a possible correlation between the angiogenesis parameter Amp (generated from DCE-MRI of vertebral BM) and EMD in patients with MM. These results identified high Amp values (>0.08) as a possible risk factor associated with the development of EMD in MM patients; high Amp values indicate high tissue vascularity and permeability. This finding partly supports the hypothesis that BM angiogenesis may play role in the development of EMD in MM. Thus, for MM patients, quantitative analysis is necessary using DCE-MRI data and angiogenesis and blood-vessel permeability based microcirculation variables. However, a fuller understanding of what these various measurements imply is necessary before such assessments can be incorporated into routine clinical practice.