Dynamic contrast-enhanced MRI for advanced esophageal cancer response assessment after concurrent chemoradiotherapy.
Conventional imaging modalities, including X-ray, computed tomography (CT) and magnetic resonance imaging (MRI), have been used to assess CRT response for esophageal cancer. These imaging modalities focus on the morphologic changes of esophageal mucosa, tumor size, and enhancement. Positron emission tomography-computed tomography is valuable to assess the volumetric change and metabolic status of tumor. Published studies have demonstrated that functional MRI can be employed as a potential method for monitoring and predicting treatment response in esophageal cancer (5-14). Functional imaging by dynamic contrast-enhanced MRI (DCE-MRI) has been investigated in recent years to assess vascular permeability. Previous studies have investigated the potential role of DCE-MRI in evaluating treatment response in head, neck, breast, oral, cervical, rectal cancers, and soft tissue sarcoma (7-14). Some studies have reported the value of DCE-MRI using pharmacokinetic parameters in patients with esophageal cancer (4, 14-16). In the literature, DCE-MRI has been used in esophageal cancer to differentiate between adenocarcinoma and squamous cell carcinoma (15), assess chemotherapy response (14), and distinguish adenocarcinoma from normal esophageal wall (16).
In this study, we aimed to investigate the performance of DCE-MRI parameters in assessing and predicting treatment response after CRT in patients with advanced esophageal cancer. We focused on evaluating treatment response between pre-CRT and post-CRT and compared complete responders and non-complete responders in a larger sample size than previously reported (14); in addition, we analyzed the changes in absolute values and and ratios of DCE-MRI parameters.
This retrospective study was approved by the institutional review board of our hospital and the requirement for written informed consent was waived due to the retrospective nature of the study. From September 2014 to December 2016, patients who had undergone esophageal DCE-MRI scanning were screened. Inclusion criteria were: pathologically confirmed advanced esophageal squamous cancer by esophagoscopy; 3.0 T DCE-MRI scanning prior to concurrent CRT (pre-CRT); 3.0 T DCE-MRI 4 weeks after CRT (post-CRT); and adequate MRI quality for analysis.
From September 2014 to December 2016, 112 patients with suspicious esophageal lesions underwent DCE-MRI. The following patients were excluded: 18 patients with T1-stage esophageal cancer or high-grade intraepithelial neoplasia, 8 patients with leiomyoma, 23 patients without pre-CRT or post-CRT MRI examinations, and 4 patients with poor image artifacts. Finally, 59 patients were included in this retrospective study (Table 1). According to Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1 (17), there were 38 patients with complete response, 9 patients with partial response, 8 patients with stable disease, and 4 patients with progressive disease. For the purpose of analysis, patients were grouped as complete response (CR) group (n=38) and non-complete response (non-CR) group (n=21).
Radiation therapy at a dose of 60 Gy (2Gy/fraction, 5 fractions/week) was delivered to primary tumor site and involved lymph nodes. Chemotherapy was performed concurrently with radiation therapy by using liposomal paclitaxel 35 mg/[m.sup.2] plus cisplatin 25 mg/[m.sup.2] administered on day 1 weekly for 6 weeks.
MRI examinations were performed on a 3.0 Tesla MRI scanner (MAGNETOM Trio-Tim; Siemens) with a 16-channel torso coil. The MRI sequences included: transverse T1-weighted imaging, transverse and sagittal T2-weighted imaging, and transverse DCE-MRI. DCE-MRI scanning included two parts: before contrast injection, transverse volume interpolated breath-hold examination (VIBE) sequences were scanned with three flip angles ([alpha]= 5[degrees],10[degrees],15[degrees]) to calculate T1 mapping; then, DCE images were acquired with VIBE sequence (repetition time, 5.22 ms; echo time, 1.81 ms; field of view, 21X28 [cm.sup.2]; matrix, 256X138; slice thickness, 3 mm; number of phases, 32; temporal resolution, 7s). A bolus of MRI contrast (Gadodiamide, Omniscan, GE HealthCare) was injected at a rate of 2.5 mL/s through a 20-gauge antecubital intravenous line at the third phase of DCE scanning. Bolus injection was performed with a MRI-compatible power injector (Spectris; Stellant MR Injection System) followed by 15 mL saline flush.
Two digestive radiologists with 5 and 9 years of experience, respectively, studied the parameters on successive magnetic resonance images in consensus. All DCE-MRI data were transferred in Digital Imaging and Communications in Medicine (DICOM) format and processed with OmniKinetics software (GE Healthcare) by extended Tofts Liner model. Individual based arterial input function (AIF) was picked for each case because it varies between individuals in reflection of cardiac output, vascular tone and renal function. Referring to T2-weighted imaging and contrast-enhanced T1-weight-ed imaging, all regions of interest (ROIs) of esophageal cancer were manually set, encompassing the entire tumor area but excluding necrosis, peripheral fat, and blood vessels. The heart motion might lead to unclear tumor border. Thus, when we drew the ROI of the tumor, we made the ROI slightly smaller in size than observed tumor size to reduce the influence of partial volume effect. Three quantitative parameters obtained from DCE-MRI: [K.sup.trans] ([min.sup.-1]), transfer constant; [K.sub.ep] ([min.sup.-1]), efflux rate constant; and [V.sub.e], ratio of extracellular-extravascular space volume to tissue volume.
All statistical analyses were performed using SPSS 21.0 statistical software (IBM Corp.). The Kolmogorov-Smirnov's test was used to determine whether the quantitative parameters are subjected to normal distribution. Normally distributed data were presented as means [+ or -] standard deviation; not normally distributed data were presented by median and range. Categorical data (including gender, location, clinical T-stage and N-stage) were presented as count and frequency and compared by chi-square test. Fisher's exact test was used when chi-square conditions were not met. Numerical normally distributed data were compared with two independent sample t test; Mann-Whitney U test was used for comparison of not normally distributed data. Paired Student's t test was used to identify significant differences of the parameters between pre-CRT and post- CRT in both CR and non-CR groups. Absolute value of change and ratio of change were calculated as follows: Change in [K.sup.trans] ([[DELTA]K.sup.trans] = post-CRT [K.sup.trans] value - pre-CRT [K.sup.trans] value); change ratio of [K.sup.trans] (r[DELTA][K.sup.trans] = [DELTA][K.sup.trans] /pre-CRT [K.sup.trans] value). The same calculation method was applied to the other two parameters ([K.sub.ep] and [V.sub.e]). Independent sample t test was used to identify significant differences of the parameters between the CR and non-CR groups. Receiver operating characteristic (ROC) analyses were performed to find a reasonable threshold to differentiate CRT good responders from poor responders. The optimal thresholds were obtained by calculating the maximal Youden index (Youden index = sensitivity + specificity-1). Meanwhile, the areas under the curve (AUCs) were compared using nonparametric methods for comparison of ROC curves. Comparisons were considered statistically significant for P < 0.05.
The demographic data of all patients are summarized in Table 1. There were 26 males (mean age, 61.8[+ or -]10.1 years) and 12 females (mean age, 65.9[+ or -]6.7 years) in the CR group, 16 males (mean age, 67.5[+ or -]8.6 years) and 5 females (mean age, 65.4[+ or -]6.0 years) in the non-CR group. No statistically significant difference was identified in gender, age, and location of esophageal cancer between the CR and non-CR groups. There was significant difference in clinical T-stage (P = 0.032) between the CR and non-CR groups, while no difference was observed in clinical N-stage (P = 0.212).
Comparisons of DCE-MRI parameters between pre-CRT and post-CRT are shown in Table 2. Both [K.sup.trans] and [K.sub.ep] significantly decreased from pre-CRT to post-CRT in the CR group (P < 0.001). The [K.sub.ep] value also showed a marked reduction in the non-CR group (P = 0.028). [K.sup.trans] also decreased in the non-CR group, but it did not approach statistical significance (P = 0.199). Although [V.sub.e] values increased after CRT in both groups, the differences were not significant. Representative cases of the CR and non-CR groups are presented in Figs. 1 and 2, respectively. On pseudocolor images, warm colors imply a higher value of the parameter, while cool colors imply lower values.
Table 3 shows comparisons of DCE-MRI parameters between the CR and non-CR groups in unpaired analysis. In pre-CRT measurements, the [K.sup.trans] values of the CR group were significantly higher than that of the non-CR group (P = 0.047). In assessment of treatment response to CRT, post-[K.sup.trans] and post-[K.sub.ep] values were significantly lower in the CR group than in the non-CR group (P = 0.002, P < 0.001). The changes in value and ratios of [K.sup.trans] ([DELTA][K.sup.trans], r[DELTA][K.sup.trans]) and [K.sub.ep] ([DELTA][K.sub.ep'], r[DELTA][K.sub.ep]) showed significant difference between the CR and non-CR groups. From pre-CRT to post-CRT, the [K.sup.trans] values showed tendency to decrease in both CR and non-CR groups (35% and 2.7% reduction, respectively). The [K.sub.ep] values showed 41.6% decrease in the CR group and 6.4% in the non-CR group. The post-[V.sub.e] values were lower when compared with pre-[V.sub.e] in both groups, without reaching statistical significance. The performance of [K.sup.trans], [K.sub.ep] and [V.sub.e] parameters in predicting treatment response were assessed by ROC curve analysis (Table 4). In comparison with the other pre-CRT parameters, pre-[K.sup.trans] values indicated good diagnostic performance (AUC=0.678). For post-CRT measurements, post-[K.sub.ep] showed the highest AUC of 0.817, with a cutoff value of 1.031, sensitivity of 94.7%, and specificity of 57.1%. In terms of change, the AUC of [DELTA][K.sup.trans] was highest at 0.816, with an optimal cutoff value of -0.206, sensitivity of 52.6%, and specificity of 95.2%. In terms of ratio of change, r[DELTA][K.sup.trans] resulted in the highest AUC of 0.840, with the optimal cutoff value of -0.144, sensitivity of 89.5%, and specificity of 61.9%. ROC curves of diagnostic performance of the parameters for detecting CRT response were shown in Fig. 3.
DCE-MRI is a widely used imaging method reflecting vascular perfusion and endothelial permeability of tumor microcirculation, which are regarded as the most important factors in assessment of CRT response. This study investigated the role of quantitative DCE-MRI parameters of preand post-CRT to assess and predict treatment response for patients with advanced esophageal cancer.
Our data showed that there was significant difference in clinical T-stage between the CR and non-CR groups, while no changes were observed in clinical N-stage, gender, age, and location of tumor. The percentage of clinical T2 stage patients in the non-CR group was lower than that in the CR group, suggesting that patients with higher T-stage esophageal cancer might have a poorer CRT response. Consistent with studies on oral cancer and esophageal cancer, our results also demonstrated that an advanced T-stage indicated a poor clinical response (10, 16).
The [K.sup.trans] and K values are closely associated with the degree of tumor microcirculation and angiogenesis. Compared with normal blood vessels, tumor neovascularization leads to increased permeability and perfusion, which means higher [K.sup.trans] and [K.sub.ep] values. Before CRT, the [K.sup.trans] value was significantly higher in the CR group than in the non-CR group. Therefore, we assume that high pre-[K.sup.trans] value is associated with good response. Our finding is in agreement with a recent study in patients with esophageal cancer that has also shown better treatment response with higher pre-CRT [K.sup.trans] values (14). Other studies have also suggested that tumors with high [K.sup.trans] values may have better treatment response compared with those with low [K.sup.trans] values, because of better delivery of the chemotherapeutic agents and greater radiosensitivity (18-21). However, previous DCE-MRI studies were unable to show any correlation between pretreatment [K.sup.trans] values and treatment response for oral cancer and rectal cancer (10, 18). We postulate that lower [K.sup.trans] value in the non-CR group may indicate relatively lower blood perfusion which reduces the effectiveness of chemoradiation. Our observation is in accordance with previous investigations (18, 22-24). Among pre-CRT parameters, pre-[K.sup.trans] values showed the highest AUC in predicting treatment response, suggesting that it can be a promising MRI biomarker.
We also found that the [K.sup.trans] value in the CR group showed a significant decrease after CRT, a finding that corresponded well with those of previous studies (10, 22, 25). Kim et al. (22) attributed the contrasting changes and ratios of [K.sup.trans] after CRT to a larger fibrotic area in good responders, but a substantial, residual, viable tumor area in poor responders. Other studies explained the decrease of [K.sup.trans] value by lower microvessel density after CRT (23-26). This opinion also explains the increase in [V.sub.e] value after CRT, although change and ratio of [V.sub.e] value showed no statistical difference between pre- and post- CRT in this study. Our findings bear some similarities to the findings in a recent study, which revealed that higher [K.sup.trans] values before therapy, lower [K.sup.trans] values after therapy, and a large reduction in relative [K.sup.trans] indicate good response (10, 18, 20, 22). The absolute r[DELTA][K.sup.trans] of good responders in previous studies are divergent, ranging from 8.6% to 38.4% (10, 18, 20, 22). The present study revealed that the [K.sub.ep] values representing vessel permeability decreased after CRT in both groups. Among post-CRT measurements, the post-[K.sub.ep] value resulted in better diagnostic performance in assessing treatment response (AUC=0.817). Meanwhile, the absolute [DELTA][K.sub.ep] and r[DELTA][K.sub.ep] values in the CR group were significantly higher than those in the non-CR group. These findings are supported by previous studies in which the range of absolute r[DELTA][K.sub.ep] was 20.3%-37.3% (10, 20, 27, 28). However, our study is inconsistent with a previous evaluation of treatment response in 25 patients with esophageal cancer (14). We speculate that these diverse results may be associated with the sample size and tumor heterogeneity. Thus, a larger sample size is needed to verify the results, and further investigation is warranted to determine whether tumor heterogeneity affects the quantitative parameters of DCE-MRI.
Previous studies reported that CRT could cause a significant increase in the [V.sub.e] value which was associated with a better response (12, 14). A study assessing chemotherapy response in patients with osteosarcoma revealed that [V.sub.e] might serve as a prognostic biomarker (29). Whereas, our data revealed no significant change in [V.sub.e] values from preto post-CRT in the CR and non-CR groups. Other investigators also failed to find significant differences in the [V.sub.e] value between the good and poor responders (18, 22). The findings might be attributed to the effectiveness of CRT in inhibiting the generation of tumor cells, leading to increase in the extravascular extracellular space (EES) and the volumetric proportion of the EES (14). The [V.sub.e] value represents the motion space of water molecules, and is affected by blood flow. Increased blood flow can increase the contrast agent getting into the EES, so [V.sub.e] cannot be used alone to evaluate the blood perfusion and EES. [V.sub.e] is a comprehensive factor, which means that it is not definite in the evaluation of tumor angiogenesis.
Our study suffers from some limitations. First, the sample size in this present study might affect the accuracy of the results. Therefore, we need a larger sample size in further studies. Second, we did not compare DCE-MRI parameters with data from diffusion-weighted imaging (DWI). Past findings suggested that DWI could potentially provide complementary information about treatment response assessment and prediction (30, 31). Further study of the correlation analysis of DWI and DCE-MRI would be necessary for esophageal carcinoma. Finally, we did not investigate tumor heterogeneity. The diverse results in previous studies may be associated with tumor heterogeneity. Histogram analysis of DCE-MRI parameters might provide quantitative information about tumor heterogeneity.
Reportedly, some immunohistochemical, blood-based, mRNA-based, and gene expression profiling biomarkers are associated with esophageal cancer detection, diagnosis, treatment, and prognosis (32). Thus, further investigations of the correlation between the above-mentioned cancer biomarkers and MRI biomarkers are warranted.
In conclusion, our observations demonstrate that DCE-MRI parameters have the potential to assess and predict treatment response to CRT. Particularly, pre-CRT [K.sup.trans] was valuable in predicting treatment response. Moreover, marked reductions in [K.sup.trans] and [K.sub.ep] values were associated with good CRT response. Finally, in ROC analysis of diagnostic performance, r[DELTA][K.sup.trans], the ratio of change in [K.sup.trans] value, showed substantial advantage for assessing treatment response to CRT.
Conflict of interest disclosure
The authors declared no conflicts of interest.
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Na-Na Sun [iD]
Chang Liu [iD]
Xiao-Lin Ge [iD]
Jie Wang [iD]
From the Departments of Radiology (N-N.S., C.L.) and Radiotherapy (X-L.G., J.W. email@example.com), The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Received 10 October 2017; revision requested 29 October 2017; last revision received 27 February 2018; accepted 12 March 2018.
* We investigated the role of quantitative DCE-MRI parameters to assess and predict chemoradiotherapy (CRT) response for patients with advanced esophageal cancer.
* Patients with high T-stage esophageal cancer may present with poor CRT response.
* The MRI parameter [pre-K.sup.trans] is valuable in predicting treatment response to CRT.
* Marked reductions in [K.sup.trans] and [K.sub.ep] values were associated with good CRT response.
* ROC curves of diagnostic performance of [r[delta]K.sup.trans] showed substantial advantage for assessing treatment response to CRT.
Table 1. Summary of demographic data in 59 patients CR group (n=38) non-CR group (n=21) P Gender 0.528 Men 26 (68.4) 16 (76.2) Women 12 (31.6) 5 (23.8) Mean age (years) All patients 63.3[+ or -]9.3 67.1[+ or -]8.1 0.542 Men 61.8[+ or -]10.1 67.5[+ or -]8.6 0.416 Women 65.9[+ or -]6.7 65.4[+ or -]6.0 0.685 Clinical T-stage 0.032 (*) II 13 (34.2) 1 (4.8) III 16 (42.1) 11 (52.4) IV 9 (23.7) 9 (42.9) Clinical N-stage 0.212 N0 12 (31.6) 4 (19.0) N1 10 (26.3) 7 (33.3) N2 9 (23.7) 9 (42.9) N3 7 (18.4) 1 (4.8) Location 0.087 Cervical 3 (7.9) 2 (9.5) Upper thoracic 16 (42.1) 3 (14.3) Middle thoracic 15 (39.5) 10 (47.6) Distal 4 (10.5) 6 (28.6) Data are presented as n (%). CR, complete response; non-CR, non-complete response (partial response, stable disease, or progressive disease). (*) P < 0.05. Table 2. Comparison of DCE-MRI parameters between pre-CRT and post-CRT CR group pre-CRT post-CRT P [K.sup.trans] 0.576[+ or -]0.132 0.363[+ or -]0.100 <0.001 [K.sub.ep] 1.431[+ or -]0.466 0.762[+ or -]0.204 <0.001 [V.sub.e] 0.451[+ or -]0.189 0.490[+ or -]0.118 0.248 non-CR group pre-CRT post-CRT P [K.sup.trans] 0.489[+ or -]0.162 0.459[+ or -]0.127 0.219 [K.sub.ep] 1.294[+ or -]0.528 1.061[+ or -]0.263 0.028 [V.sub.e] 0.445[+ or -]0.199 0.458[+ or -]0.173 0.783 DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging; CR, complete response; non-CR, non-complete response (partial response, stable disease, or progressive disease); CRT, chemoradiation therapy; [K.sup.trans], volume transfer constant between extravascular-extracellular space and blood plasma; [K.sub.ep], rate constant from extravascular extracellular space to blood plasma; [V.sub.e], extravascular-extracellular space volume per unit tissue volume. The unit for [K.sup.trans] and [K.sub.ep] value is [min.sub.-1]. Table 3. Comparison of DCE-MRI parameters between the CR and non-CR groups Parameters CR group (n=3) non-CR group mean[+ or -]SD (n=21) mean[+ or -]SD Pre-[K.sup.trans] 0.576[+ or -]0.132 0.489[+ or -]0.162 Post-[K.sup.trans] 0.363[+ or -]0.100 0.459[+ or -]0.127 [DELTA][K.sup.trans] -0.213[+ or -]0.134 -0.040[+ or -]0.137 r[DELTA][K.sup.trans] -0.350[+ or -]0.177 -0.027[+ or -]0.334 Pre-[K.sub.ep] 1.431[+ or -]0.466 1.294[+ or -]0.528 Post-[K.sub.ep] 0.762[+ or -]0.204 1.061[+ or -]0.263 [DELTA][K.sub.ep] -0.668[+ or -]0.446 -0.232[+ or -]0.451 r[DELTA][K.sub.ep] -0.416[+ or -]0.229 -0.064[+ or -]0.376 Pre-[V.sub.e] 0.451[+ or -]0.189 0.445[+ or -]0.199 Post-[V.sub.e] 0.490[+ or -]0.118 0.458[+ or -]0.173 [DELTA][V.sub.e] 0.028[+ or -]0.202 0.014[+ or -]0.223 r[DELTA][V.sub.e] 0.234[+ or -]0.563 0.198[+ or -]0.653 Parameters P Pre-[K.sup.trans] 0.047 Post-[K.sup.trans] 0.002 (*) [DELTA][K.sup.trans] <0.001 (*) r[DELTA][K.sup.trans] <0.001 (*) Pre-[K.sub.ep] 0.308 Post-[K.sub.ep] <0.001 (*) [DELTA][K.sub.ep] 0.001 (*) r[DELTA][K.sub.ep] <0.001 (*) Pre-[V.sub.e] 0.903 Post-[V.sub.e] [DELTA][V.sub.e] 0.793 r[DELTA][V.sub.e] 0.823 The unit for [K.sup.trans] and [K.sub.ep] value is X [10.sup.-3] [mm.sup.2]/s. CRT, chemoradiation therapy; [K.sup.trans], volume transfer constant between extravascular-extracellular space and blood plasma; [K.sub.ep], rate constant from extravascular extracellular space to blood plasma; [V.sub.e] extravascular-extracellular space volume per unit tissue volume; [DELTA]X, change in X; r[DELTA]X, change ratio of X. (*) P < 0.05. Table 4. Diagnostic performance of the parameters for the detection of response to CRT Parameter AUC Sensitivity (%) Pre-[K.sup.trans] 0.678 (0.544-0.794) 68.4 (51.3-82.5) Post-[K.sup.trans] 0.719 (0.587-0.828) 68.4 (51.3-82.5) [DELTA][K.sup.trans] 0.816 (0.693-0.905) 52.6 (35.8-69.0) r[DELTA][K.sup.trans] 0.840 (0.721-0.922) 89.5 (75.2-97.0) Pre-[K.sub.ep] 0.578 (0.442-0.705) 63.2 (46.0-78.2) Post-[K.sub.ep] 0.817 (0.695-0.906) 94.7 (82.2-99.2) [DELTA][K.sub.ep] 0.757 (0.628-0.859) 65.8 (48.6-80.4) r[DELTA][K.sub.ep] 0.813 (0.690-0.903) 78.9 (62.7-90.4) Pre-[V.sup.e] 0.546 (0.411-0.676) 81.6 (65.7-92.2) Post-[V.sup.e] 0.595 (0.459-0.721) 92.1 (78.6-98.2) [DELTA][V.sub.e] 0.563 (0.428-0.692) 68.4 (51.3-82.5) r[DELTA][V.sub.e] 0.566 (0.431-0.695) 68.4 (51.3-82.5) Parameter Specificity (%) Cutoff value Pre-[K.sup.trans] 66.7 (43.0-85.4) 0.509 Post-[K.sup.trans] 66.7 (43.0-85.4) 0.403 [DELTA][K.sup.trans] 95.2 (76.1-99.2) -0.206 r[DELTA][K.sup.trans] 61.9 (38.5-81.8) -0.144 Pre-[K.sub.ep] 61.9 (38.5-81.8) 1.339 Post-[K.sub.ep] 57.1 (34.0-78.1) 1.031 [DELTA][K.sub.ep] 76.2 (52.8-91.7) -0.511 r[DELTA][K.sub.ep] 71.4 (47.8-88.6) -0.272 Pre-[V.sup.e] 47.6 (25.7-70.2) 0.349 Post-[V.sup.e] 38.1 (18.2-61.5) 0.364 [DELTA][V.sub.e] 52.4 (29.8-74.3) -0.008 r[DELTA][V.sub.e] 52.4 (29.8-74.3) -0.024 Parameter Maximal Youden index P Pre-[K.sup.trans] 35.1 0.011 Post-[K.sup.trans] 35.1 0.003 [DELTA][K.sup.trans] 47.8 <0.001 r[DELTA][K.sup.trans] 51.4 <0.001 Pre-[K.sub.ep] 25.1 0.312 Post-[K.sub.ep] 51.8 <0.001 [DELTA][K.sub.ep] 42.0 <0.001 r[DELTA][K.sub.ep] 50.3 <0.001 Pre-[V.sup.e] 29.2 0.553 Post-[V.sup.e] 30.2 0.213 [DELTA][V.sub.e] 20.8 0.414 r[DELTA][V.sub.e] 20.8 0.390 Data in parentheses indicate 95% confidence intervals. CRT, chemoradiation therapy; AUC, area under the ROC curve; [K.sup.trans], volume transfer constant between extravascular-extracellular space and blood plasma; [K.sub.ep], rate constant from extravascular extracellular space to blood plasma; [V.sub.e], extravascular-extracellular space volume per unit tissue volume; [DELTA]X, change in X; r[DELTA]X, change ratio of X.
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|Title Annotation:||ORIGINAL ARTICLE; magnetic resonance imaging|
|Author:||Sun, Na-Na; Liu, Chang; Ge, Xiao-Lin; Wang, Jie|
|Publication:||Diagnostic and Interventional Radiology|
|Date:||Jul 1, 2018|
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