Publications by authors named "Xinming Zhao"

79 Publications

The promising outcome with simultaneous integrated boost intensity modulated radiotherapy in confined nasal extranodal NK/T-cell lymphoma.

Leuk Lymphoma 2021 Jul 14:1-8. Epub 2021 Jul 14.

Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

The study aimed to retrospectively analyze the prognosis of patients with stage IE nasal extranodal natural killer/T-cell lymphoma (ENKTL) with dose reduction to clinical target volume (CTV) by using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT). Forty-four patients were reviewed retrospectively. The prescribed dose was 45 Gy/25 fractions for extended involved-field site and 50-55 Gy/25 fractions for primary tumor site by using SIB-IMRT. The 5-year overall survival (OS), local control (LC) and progression-free survival (PFS) were 81.2%, 93.0%, and 78.8%, respectively. The complete response (CR) rate was 85.4% (37/44). Three patients (6.8%) patients had local failure and 3 (6.8%) patients developed systemic failure. There was only one patient had grade 3 mucositis and 2 patients had grade 3 or grade 4 hematologic toxicities. For patients with stage IE nasal ENKTL, appropriate dose reduction to CTV by SIB-IMRT strategy is feasible and safe with a promising outcome.
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http://dx.doi.org/10.1080/10428194.2021.1948035DOI Listing
July 2021

Integrin αβ-targeted MR molecular imaging of breast cancer in a xenograft mouse model.

Cancer Imaging 2021 Jun 29;21(1):44. Epub 2021 Jun 29.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.

Background: The motif RXDLXXL-based nanoprobes allow specific imaging of integrin αβ, a protein overexpressed during tumorigenesis and tumor progression of various tumors. We applied a novel RXDLXXL-coupled cyclic arginine-glycine-aspartate (RGD) nonapeptide conjugated with ultrasmall superparamagnetic iron oxide nanoparticles (referred to as cFK-9-USPIO) for the application of integrin αβ-targeted magnetic resonance (MR) molecular imaging for breast cancer.

Methods: A novel MR-targeted nanoprobe, cFK-9-USPIO, was synthesized by conjugating integrin αβ-targeted peptide cFK-9 to N-amino (-NH2)-modified USPIO nanoparticles via a dehydration esterification reaction. Integrin αβ-positive mouse breast cancer (4 T1) and integrin αβ negative human embryonic kidney 293 (HEK293) cell lines were incubated with cFK-9-AbFlour 647 (blocking group) or cFK-9-USPIO (experimental group), and subsequently imaged using laser scanning confocal microscopy (LSCM) and 3.0 Tesla magnetic resonance imaging (MRI) system. The affinity of cFK-9 targeting αβ was analyzed by calculating the mean fluorescent intensity in cells, and the nanoparticle targeting effect was measured by the reduction of T2 values in an in vitro MRI. The in vivo MRI capability of cFK-9-USPIO was investigated in 4 T1 xenograft mouse models. Binding of the targeted nanoparticles to αβ-positive 4 T1 tumors was determined by ex vivo histopathology.

Results: In vitro laser scanning confocal microscopy (LSCM) imaging showed that the difference in fluorescence intensity between the targeting and blocking groups of 4 T1 cells was significantly greater than that in HEK293 cells (P < 0.05). The in vitro MRI demonstrated a more remarkable T2 reduction in 4 T1 cells than in HEK293 cells (P < 0.001). The in vivo MRI of 4 T1 xenograft tumor-bearing nude mice showed significant T2 reduction in tumors compared to controls. Prussian blue staining further confirmed that αβ integrin-targeted nanoparticles were specifically accumulated in 4 T1 tumors and notably fewer nanoparticles were detected in 4 T1 tumors of mice injected with control USPIO and HEK293 tumors of mice administered cFK-9-USPIO.

Conclusions: Integrin αβ-targeted nanoparticles have great potential for use in the detection of αβ-overexpressed breast cancer with MR molecular imaging.
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http://dx.doi.org/10.1186/s40644-021-00411-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244136PMC
June 2021

RECIST 1.1, Choi and mChoi criteria in the evaluation of tumor response in patients with metastatic colorectal cancer treated with Regorafenib and anti-PD-1 antibody.

Eur J Radiol 2021 Aug 10;141:109823. Epub 2021 Jun 10.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, 100021, China.

Purpose: No comparative study on evaluating performance of radiological criteria has been investigated in metastatic colorectal cancer (mCRC) patients treated with the combination of Regorafenib and anti-programmed cell death 1(PD-1) antibody. We aimed to compare the performance of different radiological criteria in evaluating response in mCRC patients treated with the combination of Regorafenib plus anti-PD-1 antibody.

Method: We retrospectively recruited patients treated with Regorafenib and anti-PD-1 antibody in a single institution. Baseline and the first tumor evaluation of contrast-enhanced computed tomography (CE-CT) were assessed by three evaluation criteria: RECIST 1.1, Choi, modified Choi (mChoi). Overall survival (OS) was defined as endpoint event.

Results: Twenty-three mCRC patients [age: 58.8 ± 10.6 years, 18 (78.3 %) males] were assessed. The median overall survival was 11.8 months. According to RECIST 1.1, 8 (34.8 %) patients were stable disease (SD) and 15 (65.2 %) were progressive disease (PD). According to Choi and mChoi, 5 (21.7 %) and 1(4.3 %) patient was responders, respectively. All non-PD patients showed significantly better overall survival than PD patients by all criteria. According to Choi, those identified as responders showed better overall survival than non-responders though significant statistics were not reached (P=0.262).

Conclusions: RECIST 1.1, Choi and mChoi criteria could identify survival benefit from Regorafenib plus anti-PD-1 antibody in mCRC patients. However, the value of responders detected by Choi remains to be validated in further studies.
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http://dx.doi.org/10.1016/j.ejrad.2021.109823DOI Listing
August 2021

Value of multiple models of diffusion-weighted imaging for improving the nodal staging of preoperatively node-negative rectal cancer.

Abdom Radiol (NY) 2021 Jun 14. Epub 2021 Jun 14.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.

Objective: To investigate the parameters of multiple diffusion-weighted imaging (DWI) models for improving nodal staging of preoperatively node-negative rectal cancer.

Materials And Methods: A total of 74 rectal cancer patients without suspected metastatic lymph nodes on conventional MRI who underwent direct surgical resection between November 2018 and January 2020 were enrolled in this prospective study. DWI parameters of mono-exponential model (ADC), intravoxel incoherent motion (D, D* and f), stretched exponential model (DDC and α), and diffusion kurtosis imaging (MD and MK) within the whole tumor were measured to predict the nodal staging in rectal cancer patients.

Results: The D*, DDC, and MK values were significantly different in patients with pN0 and pN1-2 (all P < 0.001). The D*, DDC, and MK showed good diagnostic performance with the area under the receiver operating characteristic (AUC) of 0.788, 0.827 and 0.799. Multivariate analysis indicated D* (odds ratio, OR = 1.163, P = 0.003) and DDC (OR = 0.007, P = 0.019) as significant predictors of nodal staging. The combination of DDC and D* demonstrated superior diagnostic performance with the AUC, sensitivity, specificity and accuracy of 0.872, 0.800, 0.932 and 0.878, respectively.

Conclusion: Multiple functional DWI parameters were potential to identify the rectal cancer patients with micro-nodal involvement for accurate treatment.
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http://dx.doi.org/10.1007/s00261-021-03125-5DOI Listing
June 2021

A magnetic resonance imaging (MRI)-based nomogram for predicting lymph node metastasis in rectal cancer: a node-for-node comparative study of MRI and histopathology.

Quant Imaging Med Surg 2021 Jun;11(6):2586-2597

Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The aim of the present study was to investigate the potential risk factors for lymph node metastasis (LNM) in rectal cancer using magnetic resonance imaging (MRI), and to construct and validate a nomogram to predict its occurrence with node-for-node histopathological validation.

Methods: Our prediction model was developed between March 2015 and August 2016 using a prospective primary cohort (32 patients, mean age: 57.3 years) that included 324 lymph nodes (LNs) from MR images with node-for-node histopathological validation. We evaluated multiple MRI variables, and a multivariable logistic regression analysis was used to develop the predictive nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. The performance of the nomogram in predicting LNM was validated in an independent clinical validation cohort comprising 182 consecutive patients.

Results: The predictors included in the individualized prediction nomogram were chemical shift effect (CSE), nodal border, short-axis diameter of nodes, and minimum distance to rectal cancer or rectal wall. The nomogram showed good discrimination (C-index: 0.947; 95% confidence interval: 0.920-0.974) and good calibration in the primary cohort. Decision curve analysis confirmed the clinical usefulness of the nomogram in predicting the status of each LN. For the prediction of LN status in the clinical validation cohort by readers 1 and 2, the areas under the curves using the nomogram were 0.890 and 0.841, and the areas under the curves of readers using their experience were 0.754 and 0.704, respectively. Diagnostic efficiency was significantly improved by using the nomogram (P<0.001).

Conclusions: The nomogram, which incorporates CSE, nodal location, short-axis diameter, and minimum distance to rectal cancer or rectal wall, can be conveniently applied in clinical practice to facilitate the prediction of LNM in patients with rectal cancer.
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http://dx.doi.org/10.21037/qims-20-1049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107309PMC
June 2021

Prognostic risk factors and survival models for T3 locally advanced rectal cancer: what can we learn from the baseline MRI?

Eur Radiol 2021 Jul 18;31(7):4739-4750. Epub 2021 May 18.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Objectives: To evaluate the baseline MRI characteristics for predicting survival outcomes and construct survival models for risk stratification to facilitate personalized treatment and follow-up strategies in patients with MRI-defined T3 (mrT3) locally advanced rectal cancer (LARC).

Methods: We retrospectively reviewed 256 mrT3 LARC patients evaluated between 2008 and 2012 in our institution, with an average follow-up period of 6.8 ± 1.2 years. The baseline MRI characteristics, clinical data, and follow-up information were evaluated. The patients were randomized into a training cohort (TC, 186 patients) and validation cohort (VC, 70 patients). The TC dataset was used to develop multivariate nomograms for disease-free survival (DFS) and overall survival (OS), while the VC dataset was used for independent validation of the models. Harrell concordance (C) indices and Hosmer-Lemeshow calibration were used to evaluate the performances of the models.

Results: Baseline mrT3 substage, extramural venous invasion (EMVI) grading, mucinous adenocarcinoma, mesorectal fascia involvement, elevated pretreatment carcinoembryonic antigen level, and neoadjuvant chemoradiotherapy (NCRT) were independent predictors of DFS. T3 substage, EMVI grading, and NCRT were also independent predictors of OS. The nomograms constructed permitted the individualized prediction of 3-year and 5-year DFS and 5-year OS with high discrimination (C-index range, 0.833-0.892) and good calibration in the TC and VC.

Conclusions: We have identified baseline MRI characteristics that help independently predict survival outcomes in patients with mrT3 LARC. The survival models based on these characteristics allow for the individualized pretreatment risk stratification in patients with mrT3 LARC.

Key Points: • Baseline MRI characteristics can independently stratify risk and predict survival outcomes in patients with mrT3 LARC. • The nomograms built using selected baseline MRI characteristics facilitate the individualized pretreatment risk stratification and help with clinical decision-making in patients with mrT3 LARC. • MR-defined risk factors should, therefore, be carefully reported in the baseline MRI evaluation.
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http://dx.doi.org/10.1007/s00330-021-08045-yDOI Listing
July 2021

Preoperative volumetric synthetic magnetic resonance imaging of the primary tumor for a more accurate prediction of lymph node metastasis in rectal cancer.

Quant Imaging Med Surg 2021 May;11(5):1805-1816

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: An accurate assessment of lymph node (LN) status in patients with rectal cancer is important for treatment planning and an essential factor for predicting local recurrence and overall survival. In this study, we explored the potential value of histogram parameters of synthetic magnetic resonance imaging (SyMRI) in predicting LN metastasis in rectal cancer and compared their predictive performance with traditional morphological characteristics and chemical shift effect (CSE).

Methods: A total of 70 patients with pathologically proven rectal adenocarcinoma who received direct surgical resection were enrolled in this prospective study. Preoperative rectal MRI, including SyMRI, were performed, and morphological characteristics and CSE of LN were assessed. Histogram parameters were extracted on a T1 map, T2 map, and proton density (PD) map, including mean, variance, maximum, minimum, 10th percentile, median, 90th percentile, energy, kurtosis, entropy, and skewness. Receiver operating characteristic (ROC) curves were used to explore their predictive performance for assessing LN status.

Results: Significant differences in the energy of the T1, T2, and PD maps were observed between LN-negative and LN-positive groups [all P<0.001; the area under the ROC curve (AUC) was 0.838, 0.858, and 0.823, respectively]. The maximum and kurtosis of the T2 map, maximum, and variance of PD map could also predict LN metastasis with moderate diagnostic power (P=0.032, 0.045, 0.016, and 0.047, respectively). Energy of the T1 map [odds ratio (OR) =1.683, 95% confidence interval (CI): 1.207-2.346, P=0.002] and extramural venous invasion on MRI (mrEMVI) (OR =10.853, 95% CI: 2.339-50.364, P=0.002) were significant predictors of LN metastasis. Moreover, the T1 map energy significantly improved the predictive performance compared to morphological features and CSE (P=0.0002 and 0.0485).

Conclusions: The histogram parameters derived from SyMRI of the primary tumor were associated with LN metastasis in rectal cancer and could significantly improve the predictive performance compared with morphological features and CSE.
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http://dx.doi.org/10.21037/qims-20-659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047345PMC
May 2021

Prediction of false-negative extramural venous invasion in patients with rectal cancer using multiple mathematical models of diffusion-weighted imaging.

Eur J Radiol 2021 Jun 22;139:109731. Epub 2021 Apr 22.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. No.17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. Electronic address:

Purpose: To investigate the parameters from mono-exponential, stretched-exponential, and intravoxel incoherent motion diffusion-weighted imaging (DWI) models for evaluating false-negative extramural venous invasion (EMVI) on conventional magnetic resonance imaging (MRI) in rectal cancer patients.

Material And Methods: Seventy-two rectal cancer patients with negative EMVI on conventional MRI who underwent direct surgical resection were enrolled in this prospective study. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), distributed diffusion coefficient (DDC), and water molecular diffusion heterogeneity index (α) values within the whole tumor were obtained to identify the patients with false-negative EMVI. Receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic performance. Multivariate binary logistic regression analysis was conducted to determine the independent risk factors.

Results: The DDC, D*, f, and α values were significantly different in the EMVI-positive and EMVI-negative groups (P =  0.018, and P <  0.001, respectively). The D*, f, and α values demonstrated good diagnostic performance with area under the ROC curve (AUC) of 0.861, 0.824, and 0.854, respectively. The combined model, including D*, α, and tumor location, proved superior diagnostic performance with the AUC, sensitivity, specificity, and accuracy of 0.971, 0.917, 0.967, and 0.931, respectively. The AUC of the combined model was significantly higher than that of the D*, f, and DDC (P = 0.004, 0.045, and 0.002, respectively).

Conclusion: Multi-b-value DWI may be a potential tool for identifying micro-EMVI in rectal cancer. The combination of DWI parameters and tumor location leads to superior diagnostic performance.
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http://dx.doi.org/10.1016/j.ejrad.2021.109731DOI Listing
June 2021

Improving deformable image registration with point metric and masking technique for postoperative breast cancer radiotherapy.

Quant Imaging Med Surg 2021 Apr;11(4):1196-1208

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Deformable image registration (DIR) is increasingly used for target volume definition in radiotherapy. However, this method is challenging for postoperative breast cancer patients due to the large deformations and non-correspondence caused by tumor resection and clip insertion. In this study, an improved B-splines based DIR method was developed to address this issue for higher registration accuracy.

Methods: The conventional B-splines based DIR method was improved with the introduction of point metric and masking technique. The point metric minimizes the distance between 2 point sets with known correspondence for regularization of intensity-based B-splines registration. The masking technique reduces the influence of non-corresponding regions in breast computed tomography (CT) images. Two sets of CT images before and after breast surgery were used for image registration. One set was the diagnostic CT image acquired before surgery, and another set was the planning CT image acquired after surgery for breast cancer radiotherapy. A total of 26 sets of CT images from 13 patients were collected retrospectively for the test. The improved DIR method's registration accuracy was evaluated by target registration error (TRE), the Jacobian determinant, and visual assessment.

Results: For soft tissue, the difference in the median TRE between the improved DIR method and the conventional DIR method was statistically significant (2.27 5.88, P<0.05). The Jacobian determinant of the deformation field was positive for all patients. For visual assessment, the improved DIR method with point metric achieved better matching for soft tissue.

Conclusions: The improved DIR method's registration accuracy was higher than the conventional DIR method based on the preliminary results. With point metric and masking technique, the influence of large deformations and non-correspondence on registration between pre- and post-operative CT images can be effectively reduced. Therefore, this method provides a feasible way for target volume definition in postoperative breast cancer radiotherapy treatment planning.
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http://dx.doi.org/10.21037/qims-20-705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930685PMC
April 2021

Prediction of pathological prognostic factors of rectal cancer by relaxation maps from synthetic magnetic resonance imaging.

Eur J Radiol 2021 May 15;138:109658. Epub 2021 Mar 15.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. Electronic address:

Purpose: To explore the feasibility of relaxation maps from synthetic MRI for predicting pathological prognostic factors of rectal cancer (RC) and to compare the predictive performance of quantitative values and conventional subjective evaluation.

Material And Methods: A total of 94 patients with pathologically proven RC who underwent direct surgical resection were enrolled in this prospective study. Preoperative rectal MRI including synthetic MRI was performed. The mean T, T, and PD value of the whole tumor was obtained to preoperatively assess the pathological T stage, N stage, extramural venous invasion (EMVI), differentiation, and perineural invasion. Receiver operating characteristic curves were used to explore the predictive performance for assessing the prognostic factors. The T stage, N stage and EMVI status on conventional T2WI were evaluated and compared with the quantitative values.

Results: The T value decreased significantly in patients with positive perineural invasion, lymph node metastasis (LNM), EMVI, and higher T stage RC (p =  0.007 and < 0.001). The T value of LNM and EMVI positive groups was significantly lower than those of the negative groups (p =  0.034 and 0.011). For predicting N stage and EMVI, the T value demonstrated good performance with an AUC of 0.883 (95 % confidence interval, CI, 0.801-0.940) and 0.821 (95 % CI, 0.729-0.893); the T value was superior to the T value and subjective evaluation of radiologists (all p < 0.05).

Conclusion: Synthetic MRI is a promising tool for noninvasive evaluation of prognostic factors of RC by generating relaxation maps.
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http://dx.doi.org/10.1016/j.ejrad.2021.109658DOI Listing
May 2021

Preoperative evaluation of extramural venous invasion in rectal cancer using radiomics analysis of relaxation maps from synthetic MRI.

Abdom Radiol (NY) 2021 Aug 20;46(8):3815-3825. Epub 2021 Mar 20.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: To establish a radiomics nomogram based on relaxation maps for predicting the extramural venous invasion (EMVI) of rectal cancer (RC) and compare the diagnostic efficacy of the nomogram and subjective assessment by radiologists.

Material And Methods: Among 94 RC patients receiving direct surgical resection, 65 were randomly allocated to the training cohort and 29 to the validation cohort. Radiomics features were extracted from synthetic magnetic resonance imaging including T1, T2, and proton density (PD) maps. The least absolute shrinkage and selection operator methods were used for dimension reduction, feature selection, and radiomics model building. Multivariable logistic regression analysis was used for nomogram development. The performance of the nomogram was assessed with respect to its calibration, receiver operating characteristics (ROC) curve, and decision curve analysis.

Results: The radiomics model demonstrated good predictive efficacy for EMVI, with an area under the ROC curve (AUC), sensitivity, and specificity of 0.912 (95% confidence interval (CI), 0.837-0.986), 0.824, and 0.875 in the training cohort and 0.877 (95% CI 0.751-1.000), 0.833, and 0.826 in the validation cohort. The nomogram had good diagnostic performance, with AUCs of 0.925 (95% CI 0.862-0.988) and 0.899 (95% CI 0.782-1.000) in the training and validation cohort. Furthermore, the radiomics signature showed better diagnostic efficiency than the subjective assessment by both readers (AUC =0.912 vs. 0.732 and 0.763, P = 0.023 and 0.028, respectively).

Conclusion: A radiomics nomogram was developed to preoperatively predict EMVI in RC patients. The application of the radiomics model based on relaxation maps could improve the diagnostic efficacy of EMVI.
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http://dx.doi.org/10.1007/s00261-021-03021-yDOI Listing
August 2021

Integrating Lung Parenchyma Segmentation and Nodule Detection with Deep Multi-task Learning.

IEEE J Biomed Health Inform 2021 Jan 20;PP. Epub 2021 Jan 20.

Lung parenchyma segmentation is valuable for improving the performance of lung nodule detection in computed tomography (CT) images. Traditionally, the two tasks are performed separately. This paper proposes a deep multi-task learning (MTL) approach to integrate these tasks for better lung nodule detection. Three new ideas lead to our proposed approach. First, lung parenchyma segmentation is used as the attention module and is combined with nodule detection in a single deep network. Second, lung nodule detection is performed in an anchor-free manner by dividing it into two subtasks, nodule center identification and nodule size regression. Third, a novel pyramid dilated convolution block (PDCB) is proposed to utilize the advantage of dilated convolution and tackle its gridding problem for better lung parenchyma segmentation. Based on these ideas, we design our end-to-end deep network architecture and corresponding MTL method to achieve lung parenchyma segmentation and nodule detection simultaneously. We evaluate the proposed approach on the commonly used Lung Nodule Analysis 2016 (LUNA16) dataset. The experimental results show the value of our contributions and demonstrate that our approach can yield significant improvements compared with state-of-the-art counterparts.
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http://dx.doi.org/10.1109/JBHI.2021.3053023DOI Listing
January 2021

Whole-tumor texture model based on diffusion kurtosis imaging for assessing cervical cancer: a preliminary study.

Eur Radiol 2021 Aug 19;31(8):5576-5585. Epub 2021 Jan 19.

Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Objectives: To evaluate the diagnostic potential of diffusion kurtosis imaging (DKI) functional maps with whole-tumor texture analysis in differentiating cervical cancer (CC) subtype and grade.

Methods: Seventy-six patients with CC were enrolled. First-order texture features of the whole tumor were extracted from DKI and DWI functional maps, including apparent kurtosis coefficient averaged over all directions (MK), kurtosis along the axial direction (Ka), kurtosis along the radial direction (Kr), mean diffusivity (MD), fractional anisotropy (FA), and ADC maps, respectively. The Mann-Whitney U test and ROC curve were used to select the most representative texture features. Models based on each individual and combined functional maps were established using multivariate logistic regression analysis. Conventional parameters-the average values of ADC and DKI parameters derived from the conventional ROI method-were also evaluated.

Results: The combined model based on Ka, Kr, MD, and FA maps yielded the best diagnostic performance in discrimination of cervical squamous cell cancer (SCC) and cervical adenocarcinoma (CAC) with the highest AUC (0.932). Among individual functional map derived models, Kr map-derived model showed the best performance when differentiating tumor subtypes (AUC = 0.828). MK_90th percentile was useful for distinguishing high-grade and low-grade in SCC tumors with an AUC of 0.701. The average values of MD, FA, and ADC were significantly different between SCC and CAC, but no conventional parameters were useful for tumor grading.

Conclusions: The whole-tumor texture analysis applied to DKI functional maps can be used for differential diagnosis of cervical cancer subtypes and grading SCC.

Key Points: • The whole-tumor texture analysis applied to DKI functional maps allows accurate differential diagnosis of CC subtype and grade. • The combined model derived from multiple functional maps performs significantly better than the single models when differentiating tumor subtypes. • MK_90th percentile was useful for distinguishing poorly and well-/moderately differentiated SCC tumors with an AUC of 0.701.
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http://dx.doi.org/10.1007/s00330-020-07612-zDOI Listing
August 2021

Impact of preset and postset adaptive statistical iterative reconstruction-V on image quality in nonenhanced abdominal-pelvic CT on wide-detector revolution CT.

Quant Imaging Med Surg 2021 Jan;11(1):264-275

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Adaptive statistical iterative reconstruction-V technique (ASIR-V) is usually set at different strengths according to the different clinical requirements and scenarios encountered when setting scanning protocols, such as setting a more aggressive tube current reduction (defined as preset ASIR-V). Reconstruction with ASIR-V is useful after scanning using image algorithms to improve image quality (defined as postset ASIR-V). The aim of this study was to investigate the quality of images reconstructed with preset and postset ASIR-V, using the same noncontrast abdominal-pelvic computed tomography (CT) protocols in the same individual on a wide detector CT.

Methods: We prospectively enrolled 141 patients. The scan protocols in Groups A-E were 0%, 20%, 40%, 60%, and 80% preset ASIR-V, respectively, in the 256 wide-detector row Revolution CT (GE Healthcare, Waukesha, WI, USA). Each group was further divided into 5 subgroups with 0%, 20%, 40%, 60%, and 80% postset ASIR-V, respectively. The 64-detector Discovery 750 HDCT (GE, USA) was used for Group F as a control group, using 0%, 20%, 40%, 60%, and 80% ASIR, respectively. Image noise was measured in the spleen, aorta, and muscle. The CT attenuation and image noise were analyzed using the paired -test; analysis of variance and post hoc multiple comparisons were made using the Student-Newman-Keuls (SNK) method.

Results: The CT attenuation in Groups A-F exhibited no significant difference between subgroups in three organs (P>0.05). Only with increasing preset ASIR-V% (Groups A to E), did the image noise decrease, except in Group B in the aorta and muscle (Noise > Noise, P=0.233, P=0.796). Only with increasing postset ASIR-V or ASIR% (Groups A and F), did the image noise decrease in the three organs. After preset and postset ASIR-V were combined, with preset ASIR-V% being equal to postset ASIR-V%, the image become similar to the corresponding preset ASIR-V part with the line of postset ASIR-V 0% (baseline of each group). When preset ASIR-V% was greater than the postset ASIR-V%, the image noise was higher than the baseline of each group. When preset ASIR-V% was less than the postset ASIR-V%, the image noise was lower than the baseline of each group. The radiation dose from B to E decreased from 11.2% to 57.1%. The CT dose index volume (CTDI) and dose length product (DLP) in Group F were significantly higher than those in Group A.

Conclusions: Using both preset and postset ASIR-V allows dose reduction, with a potential to improve image quality only when postset ASIR-V% is higher than or equal to preset ASIR-V%. The image quality depends on postset ASIR-V%, whereas the decrease of radiation dose depends on preset ASIR-V%.
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http://dx.doi.org/10.21037/qims-19-945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719942PMC
January 2021

MRI-based delta-radiomics are predictive of pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Acad Radiol 2020 Nov 11. Epub 2020 Nov 11.

Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, #17 Panjiayuan nanli, Chaoyang district, Beijing, China, 100021. Electronic address:

Rationale And Objectives: To investigate the capability of delta-radiomics to predict pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).

Materials And Methods: This retrospective study enrolled 165 consecutive patients with LARC (training set, n = 116; test set, n = 49) who received nCRT before surgery. All patients underwent pre- and post-nCRT MRI examination from which radiomics features were extracted. A delta-radiomics feature was defined as the percentage change in a radiomics feature from pre- to post-nCRT MRI. A data reduction and feature selection process including the least absolute shrinkage and selection operator algorithm was performed for building T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) delta-radiomics signature. Logistic regression was used to build a T2WI and DWI combined radiomics model. Receiver operating characteristic analysis was performed to assess diagnostic performance. Delong method was used to compare the performance of delta-radiomics model with that of magnetic resonance tumor regression grade (mrTRG).

Results: Twenty-seven of 165 patients (16.4%) achieved pCR. T2WI and DWI delta-radiomics signature, and the combined model showed good predictive performance for pCR. The combined model achieved the highest areas under the receiver operating characteristic curves of 0.91 (95% confidence interval: 0.85-0.98) and 0.91 (95% confidence interval: 0.83-0.99) in the training and test sets, respectively (significantly greater than those for mrTRG; training set, p < 0.001; test set, p = 0.04).

Conclusion: MRI-based delta-radiomics can help predict pCR after nCRT in patients with LARC with better performance than mrTRG.
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http://dx.doi.org/10.1016/j.acra.2020.10.026DOI Listing
November 2020

Non-invasive decision support for NSCLC treatment using PET/CT radiomics.

Nat Commun 2020 10 16;11(1):5228. Epub 2020 Oct 16.

Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Two major treatment strategies employed in non-small cell lung cancer, NSCLC, are tyrosine kinase inhibitors, TKIs, and immune checkpoint inhibitors, ICIs. The choice of strategy is based on heterogeneous biomarkers that can dynamically change during therapy. Thus, there is a compelling need to identify comprehensive biomarkers that can be used longitudinally to help guide therapy choice. Herein, we report a F-FDG-PET/CT-based deep learning model, which demonstrates high accuracy in EGFR mutation status prediction across patient cohorts from different institutions. A deep learning score (EGFR-DLS) was significantly and positively associated with longer progression free survival (PFS) in patients treated with EGFR-TKIs, while EGFR-DLS is significantly and negatively associated with higher durable clinical benefit, reduced hyperprogression, and longer PFS among patients treated with ICIs. Thus, the EGFR-DLS provides a non-invasive method for precise quantification of EGFR mutation status in NSCLC patients, which is promising to identify NSCLC patients sensitive to EGFR-TKI or ICI-treatments.
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http://dx.doi.org/10.1038/s41467-020-19116-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567795PMC
October 2020

Synthesis of a novel Tc labeled GE11 peptide for EGFR SPECT imaging.

Int J Radiat Biol 2020 11 1;96(11):1443-1451. Epub 2020 Sep 1.

Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Purpose: This study investigated a novel SPECT agent for the noninvasive imaging of EGFR-overexpressing tumors.

Methods: The EGFR-targeting peptide GE11 was synthesized with the introduction of four amino acids (GGGC) to its C-terminal to act as a strong chelator and radiolabeled using Tc. The radiochemical yield of the Tc-peptide-GE11 were evaluated using RP-HPLC. Cellular assays of the probe were performed on two NSCLC cell lines: A549 (high expression) and H23 (low expression). Biodistribution and SPECT imaging were performed in BALB/c nude mice bearing A549 and H23 NSCLC xenografts.

Results: The Tc-peptide-GE11 was prepared at high efficiency with radiochemical yield of 98.40 ± 1.00 % and it showed favorable stability. The cellular uptake was significantly higher in A549 than in H23 at all time points (especially at 1 h, which was 10.34 ± 0.72 and 2.04 ± 0.18, respectively). A nearly 56% reduction in probe uptake was observed after pretreatment with excess unlabeled peptides. The performance of SPECT imaging and biodistribution demonstrated higher uptake of the Tc-peptide-GE11 in A549 xenograft than in H23 xenografts.

Conclusion: The new SPECT tracer c-peptide-GE11 showed EGFR specificity, favorable pharmacokinetics and great potential for EGFR-targeted imaging.
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http://dx.doi.org/10.1080/09553002.2020.1811419DOI Listing
November 2020

Quantified MRI and 25OH-VitD3 can be used as effective biomarkers for patients with neoadjuvant chemotherapy-induced liver injury in CRCLM?

BMC Cancer 2020 Aug 15;20(1):767. Epub 2020 Aug 15.

Department of imaging diagnosis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Background: To evaluate proton-density fat-fraction (PDFF) and intravoxel incoherent motion (IVIM) techniques, and human 25-hydroxyvitamin D3 (25OH-VitD3) levels, as potential biomarkers in patients with colorectal cancer with liver metastasis (CRCLM). Changes were compared with those related to chemotherapy-associated steatohepatitis (CASH) and sinusoidal obstruction syndrome (SOS).

Methods: 63 patients with pathologically confirmed colorectal adenocarcinoma received 4-6 courses of NC before liver resection and underwent magnetic resonance imaging (MRI) with iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification and IVIM sequences. Blood samples were analyzed using CTCAE. Pathological changes of liver tissues outside the metastases were assessed as the gold standard, and receiver operating characteristic (ROC) curves were analyzed.

Results: 16 cases had CASH liver injury, 14 cases had SOS changes, and 4 cases had CASH and SOS, and 7 showed no significant changes. Consistency between biochemical indices and pathological findings was poor (kappa = 0.246, p = 0.005). The areas under the ROC curve (AUCs) of ALT, AST, ALP, GGT, and TBIL were 0.571-0.691. AUCs of D, FF, and 25OH-VitD3 exceeded 0.8; when considering these markers together, sensitivity was 85.29% and specificity was 93.13%. ANOVA showed statistically significant differences among D, FF, and 25OH-VitD3 for different grades of liver injury (F = 4.64-26.5, p = 0.000-0.016).

Conclusions: D, FF, and 25OH-VitD3 are biomarkers for accurate prediction of NC-induced liver injury in patients with CRCLM, while FF and 25OH-VitD3 might be beneficial to distinguish liver injury grades.

Trial Registration: Current Trials was retrospectively registered as ChiCTR1800015242 at Chinese Clinical Trial Registry on March 16, 2018.
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http://dx.doi.org/10.1186/s12885-020-07282-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429712PMC
August 2020

F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Metabolic Parameters Before and After Neoadjuvant Chemotherapy Can Predict the Postoperative Prognosis of Locally Advanced Gastric Cancer.

Cancer Biother Radiopharm 2020 Aug 12. Epub 2020 Aug 12.

Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

To explore the value of F-fluorodeoxyglucose positron emission tomography-computed tomography (F-FDG PET/CT) metabolic parameters before and after neoadjuvant chemotherapy in predicting histopathological response and prognosis of locally advanced gastric cancer. A total of 56 patients with locally advanced gastric cancer underwent F-FDG PET/CT before and after neoadjuvant chemotherapy. The maximum standardized uptake value (SUV), mean standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the lesions were measured before and after neoadjuvant chemotherapy. The percentage changes in the maximum standardized uptake value (ΔSUV%), mean standardized uptake value (ΔSUV%), metabolic tumor volume (ΔMTV%), and total lesion glycolysis (ΔTLG%), which were derived from F-FDG PET/CT, were calculated, and the cutoff values were determined by receiver operating characteristic curve analysis. Differences in progression-free survival (PFS) and overall survival (OS) between groups dichotomized by these cutoffs were analyzed using the Kaplan-Meier method and Cox proportional hazards regression model. The patients were divided into histopathological responders and nonresponders according to the following cutoff values: 58.8% SUV reduction, 45.8% SUV reduction, 36.9% MTV reduction, and 57.8% TLG reduction. The differences in PFS and OS between groups dichotomized by these cutoffs were significant (all  < 0.01). Multivariate analysis suggested that a ΔTLG% > 57.8% was an independent postoperative risk factor for PFS (hazard ratio [HR] 0.348, 95% confidence interval [CI] 0.131-0.926,  = 0.035) and OS (HR 0.107, 95% CI 0.023-0.498,  = 0.004). The metabolic parameters before and after neoadjuvant chemotherapy of F-FDG PET/CT accurately reflected the chemotherapy effect, and ΔTLG% was the only independent postoperative predictive factor of PFS and OS for locally advanced gastric cancer.
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http://dx.doi.org/10.1089/cbr.2020.3942DOI Listing
August 2020

Multiple mathematical models of diffusion-weighted imaging for endometrial cancer characterization: Correlation with prognosis-related risk factors.

Eur J Radiol 2020 Sep 31;130:109102. Epub 2020 May 31.

Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, China Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address:

Purpose: To investigate mono-exponential, bi-exponential, and stretched-exponential models of diffusion-weighted imaging (DWI) for evaluation of prognosis-related risk factors of endometrial cancer (EC).

Method: Sixty-one consecutive patients with EC who preoperatively underwent pelvic MRI with multiple b value DWI between September 2016 and May 2018 were enrolled. The apparent-diffusion-coefficient (ADC), bi-exponential model parameters (D, D* and f) and stretched-exponential model parameters (DDC and α) were measured and compared to analyze the following prognosis-related risk factors confirmed by pathology: histological grade, depth of myometrial invasion, cervical stromal infiltration (CSI) and lymphovascular invasion (LVSI). A stepwise multilvariate logistic regression and the receiver operating characteristic (ROC) curves were performed for further statistical analysis.

Results: Lower ADC, D, f, and DDC were observed in tumor with high grade compared with a low-grade group, and the largest area under curve (AUC) was obtained when combining f and DDC values. ADC, D, f, DDC, and α were significantly different in patients with deep myometrial invasion (DMI) compared to those without DMI; the combination of f, DDC and α showed the highest AUC. Significantly different ADC and f were found between patients' presence and absence CSI; the f values showed the highest diagnostic performance with an AUC of 0.825. Regarding the LVSI, ADC, D*, f, and DDC were significantly lower in tumors with LVSI compared to those without LVSI; the combination of f and DDC showed the largest AUC.

Conclusion: Multiple mathematical DWI models are a useful approach for the prediction of prognosis-related risk factors in EC.
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http://dx.doi.org/10.1016/j.ejrad.2020.109102DOI Listing
September 2020

Feasibility of intravoxel incoherent motion diffusion-weighted imaging in distinguishing adenocarcinoma originated from uterine corpus or cervix.

Abdom Radiol (NY) 2021 02;46(2):732-744

Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, China Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Purpose: To prospectively assess the incremental value of intravoxel incoherent motion (IVIM) DWI in determining whether the adenocarcinoma originated from the uterine corpus or cervix.

Methods: Eighty consecutive uterine adenocarcinomas from the cervix or endometrium confirmed by histopathology underwent IVIM DWI acquisition on a 3.0T MR scanner before treatment. Five morphologic features were analyzed using Fisher exact test; IVIM DWI-derived parameters, including apparent diffusion coefficient (ADC), true coefficient diffusivity (D), perfusion-related diffusivity (D), and perfusion fraction (f) were compared using two-sample independent t-test or Mann-Whitney U test. Logistic regression analysis was used to develop different diagnosis model. The ROCs of these variables and diagnostic models were compared to evaluate the diagnostic efficiency.

Results: Among single morphologic features, tumor location yielded the highest AUC of 0.891 in distinguishing endometrial adenocarcinoma (EAC) from cervical adenocarcinoma (CAC). Among single IVIM DWI-derived parameters, f values showed the best diagnostic performance (AUC: 0.837) at the optimal cut-off value of 0.261. Additionally, the combined diagnostic model, which consisted of tumor location, ADC and f showed the largest AUC of 0.967 with the highest sensitivity of 88.14%, highest specificity of 100.00%, and highest accuracy of 91.25%.

Conclusion: IVIM DWI-derived parameters add additional diagnostic value to conventional morphologic features. A combined diagnosis model is a promising imaging tool for predicting the origin of uterine adenocarcinoma, further contributing to therapeutic decision-making.
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http://dx.doi.org/10.1007/s00261-020-02586-4DOI Listing
February 2021

Value of F-FDG PET/CT radiomic features to distinguish solitary lung adenocarcinoma from tuberculosis.

Eur J Nucl Med Mol Imaging 2021 01 25;48(1):231-240. Epub 2020 Jun 25.

Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China.

Purpose: To develop a predictive model by F-FDG PET/CT radiomic features and to validate the predictive value of the model for distinguishing solitary lung adenocarcinoma from tuberculosis.

Methods: A total of 235 F-FDG PET/CT patients with pathologically or follow-up confirmed lung adenocarcinoma (n = 131) or tuberculosis (n = 104) were retrospectively and randomly divided into a training (n = 163) and validation (n = 72) cohort. Based on the Transparent Reporting of Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD), this work was belonged to TRIPOD type 2a study. The Mann-Whitney U test and least absolute shrinkage and selection operator (LASSO) algorithm were used to select the optimal predictors from 92 radiomic features that were extracted from PET/CT, and the optimal predictors were used to build the radiomic model in the training cohort. The meaningful clinical variables comprised the clinical model, and the combination of the radiomic model and clinical model was a complex model. The performances of the models were assessed by the area under the receiver operating characteristic curve (AUC) in the training and validation cohorts.

Results: In the training cohort, 9 radiomic features were selected as optimal predictors to build the radiomic model. The AUC of the radiomic model was significantly higher than that of the clinical model in the training cohort (0.861 versus 0.686, p < 0.01), and this was similar in the validation cohort (0.889 versus 0.644, p < 0.01). The AUC of the radiomic model was slightly lower than that of the complex model in the training cohort (0.861 versus 0.884, p > 0.05) and validation cohort (0.889 versus 0.909, p > 0.05), but there was no significant difference.

Conclusion: F-FDG PET/CT radiomic features have a significant value in differentiating solitary lung adenocarcinoma from tuberculosis.
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http://dx.doi.org/10.1007/s00259-020-04924-6DOI Listing
January 2021

Construction of a novel bispecific fusion protein to enhance targeting for pancreatic cancer imaging.

Biomaterials 2020 10 30;255:120161. Epub 2020 May 30.

Department of Diagnostic Imaging, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address:

Early detection and diagnosis are the most important endeavors for reducing associated morbidity and mortality of pancreatic ductal adenocarcinoma (PDAC). Developing molecular imaging probes that can specifically and effectively target cancer-associated biological pathways is one of the key points for sensitive and accurate diagnosis for PDAC. Herein, a small-sized, bispecific fusion protein constructed by genetic fusion of different binding domains of antibodies, termed Bi50, with enhanced targeting effect for PDAC is reported. Bi50 has excellent bispecific targeting for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) simultaneously in vitro and in vivo. Additionally, Bi50 shows increased intratumoral permeability and enrichment characteristics in the tumor than the control protein, which is constructed directly connecting two individual Fabs. Moreover, Bi50 can not only target areas rich in vasculature but also bind with affinity to tumor parenchymal cells, achieving "multilevel" targeting effect. Our work demonstrates that the bispecific fusion protein Bi50 has great potential as an efficient, targeted molecular imaging probe.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120161DOI Listing
October 2020

Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug Z-pemetrexed in lung adenocarcinoma Xenografts.

Invest New Drugs 2020 08 23;38(4):1031-1043. Epub 2019 Nov 23.

Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Jiankang Road, Shijiazhuang, 050011, Hebei Province, China.

Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and cytotoxic safety of the conjugate Z-pemetrexed, a novel targeted chemotherapeutic drug. In this context, human epidermal growth factor receptor 2 (HER2) + A549 lung xenografts were treated using Z-pemetrexed, pemetrexed or physiological saline. Therapeutic efficacy was monitored by single photon emission computed tomography (SPECT) imaging using the Tc-labeled Z-pemetrexed conjugate and further confirmed by performing apoptosis assays using flow cytometry analysis and hematoxylin-eosin (H&E) staining. To evaluate the expression of HER2 in tumor tissues, immunohistochemistry was performed, accompanied by quantitative analysis using flow cytometry. A toxicological evaluation was also conducted. Imaging with Tc-Z-pemetrexed demonstrated that in HER2+ A549 models, Z-pemetrexed showed better antineoplastic effects than pemetrexed. Compared with pemetrexed, the results from the pathological and flow cytometry analyses also revealed that Z-pemetrexed exhibits high antitumor activity against A549 tumors, inducing necrosis, apoptosis and cell cycle arrest. In addition, the clinical signs of toxicity in the Z-pemetrexed treated group were reduced compared with those in the pemetrexed treated group. These data revealed that the Z-pemetrexed conjugate encompasses promising targeted antitumor activity against HER2-positive lung adenocarcinoma, with reduced side effects compared with pemetrexed. Thus, the Z-pemetrexed conjugate may serve as a novel molecular agent with tremendous clinical breakthrough potential in the diagnosis and treatment of HER2-positive lung adenocarcinoma.
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http://dx.doi.org/10.1007/s10637-019-00876-3DOI Listing
August 2020

Value of pre-therapy F-FDG PET/CT radiomics in predicting EGFR mutation status in patients with non-small cell lung cancer.

Eur J Nucl Med Mol Imaging 2020 05 14;47(5):1137-1146. Epub 2019 Nov 14.

Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China.

Purpose: To assess the predictive power of pre-therapy F-FDG PET/CT-based radiomic features for epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer.

Methods: Two hundred and forty-eight lung cancer patients underwent pre-therapy diagnostic F-FDG PET/CT scans and were tested for genetic mutations. The LIFEx package was used to extract 47 PET and 45 CT radiomic features reflecting tumor heterogeneity and phenotype. The least absolute shrinkage and selection operator (LASSO) algorithm was used to select radiomic features and develop a radiomics signature. We compared the predictive performance of models established by radiomics signature, clinical variables, and their combinations using receiver operating curves (ROCs). In addition, a nomogram based on the radiomics signature score (rad-score) and clinical variables was developed.

Results: The patients were divided into a training set (n = 175) and a validation set (n = 73). Ten radiomic features were selected to build the radiomics signature model. The model showed a significant ability to discriminate between EGFR mutation and EGFR wild type, with area under the ROC curve (AUC) equal to 0.79 in the training set, and 0.85 in the validation set, compared with 0.75 and 0.69 for the clinical model. When clinical variables and radiomics signature were combined, the AUC increased to 0.86 (95% CI [0.80-0.91]) in the training set and 0.87 (95% CI [0.79-0.95]) in the validation set, thus showing better performance in the prediction of EGFR mutations.

Conclusion: The PET/CT-based radiomic features showed good performance in predicting EGFR mutation in non-small cell lung cancer, providing a useful method for the choice of targeted therapy in a clinical setting.
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http://dx.doi.org/10.1007/s00259-019-04592-1DOI Listing
May 2020

Multiplanar MRI-Based Predictive Model for Preoperative Assessment of Lymph Node Metastasis in Endometrial Cancer.

Front Oncol 2019 9;9:1007. Epub 2019 Oct 9.

Department of Diagnostic Imaging, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Assessment of lymph node metastasis (LNM) is crucial for treatment decision and prognosis prediction for endometrial cancer (EC). However, the sensitivity of the routinely used magnetic resonance imaging (MRI) is low in assessing normal-sized LNM (diameter, 0-0.8 cm). We aimed to develop a predictive model based on magnetic resonance (MR) images and clinical parameters to predict LNM in normal-sized lymph nodes (LNs). A total of 200 retrospective patients were enrolled and divided into a training cohort ( = 140) and a test cohort ( = 60). All patients underwent preoperative MRI and had pathological result of LNM status. In total, 4,179 radiomic features were extracted. Four models including a clinical model, a radiomic model, and two combined models were built. Area under the receiver operating characteristic (ROC) curves (AUC) and calibration curves were used to assess these models. Subgroup analysis was performed according to LN size. All patients underwent surgical staging and had pathological results. All of the four models showed predictive ability in LNM. One of the combined models, Model, consisting of radiomic features, LN size, and cancer antigen 125, showed the best discrimination ability on the training cohort [AUC, 0.892; 95% confidence interval [CI], 0.834-0.951] and test cohort (AUC, 0.883; 95% CI, 0.786-0.980). The subgroup analysis showed that this model also indicated good predictive ability in normal-sized LNs (0.3-0.8 cm group, accuracy = 0.846; <0.3 cm group, accuracy = 0.849). Furthermore, compared with the routinely preoperative MR report, the sensitivity and accuracy of this model had a great improvement. A predictive model was proposed based on MR radiomic features and clinical parameters for LNM in EC. The model had a good discrimination ability, especially for normal-sized LNs.
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http://dx.doi.org/10.3389/fonc.2019.01007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794606PMC
October 2019

Multi-b-value diffusion weighted imaging for preoperative evaluation of risk stratification in early-stage endometrial cancer.

Eur J Radiol 2019 Oct 12;119:108637. Epub 2019 Aug 12.

Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address:

Purpose: To investigate the application of multi-b-value DWI parameters for the assessment of risk stratification in early-stage endometrial cancer (EC).

Material And Methods: Fifty-three patients with early-stage EC who preoperatively underwent multi-b-value DWI with 13 b values (from 0 to 2000s/mm²) were included in this study. Multi-b-value DWI derived parameters, including apparent diffusion coefficient (ADC), true diffusivity (D), perfusion-related diffusivity (D*) and perfusion fraction (f) were measured independently by two radiologists. In addition, binary logical regression model was used to calculate predicative probability of combined parameters indicating statistical significance in differentiating risk stratification of early-stage endometrial cancer. Receiver operating characteristic analysis was performed for all single and combined parameters.

Results: The ADC and D values were significantly lower in intermedium-risk compared with low-risk (P = 0.000 and 0.011), as well as high-risk compared with low-risk of early-stage EC (P = 0.001 and 0.013), while f values only showed significant differences between low-risk and intermedium-risk groups (P = 0.011). Among the single parameters, the ADC values had the highest area under the ROC curve (AUC) in the identification of the low-risk of early-stage EC (AUC=0.892). Moreover, the combination of ADC and f value had the best diagnostic performance with the AUC of 0.912, the sensitivity of 81.1% and the specificity of 87.5%.

Conclusion: The multi-b-value DWI parameters provide valuable imaging biomarkers for the assessment of risk stratification in early-stage endometrial cancer. This approach might facilitate the selection of the optimal therapeutic approach and lead to the greater personalization of cancer care.
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http://dx.doi.org/10.1016/j.ejrad.2019.08.006DOI Listing
October 2019

Imaging Characteristics of USPIO Nanoparticles (<5 nm) as MR Contrast Agent and in the Liver of Rats.

Contrast Media Mol Imaging 2019 21;2019:3687537. Epub 2019 Jul 21.

Diagnostic Radiology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

Iron nanoparticles have an increasingly more and more important role in MR molecular imaging due to their novel magnetic and surface chemical properties. They provide new possibilities for noninvasive diagnosis and treatment monitoring, especially for tissues that are rich in macrophages. The smaller size and prolongation of the plasma half-life change the fate of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles captured by liver in reticuloendothelial system (RES) or mononuclear phagocytic system (MPS). However, there is still a lack of MR imaging studies on the liver assessing USPIO nanoparticles <5 nm in size to reflect its absorption and clearance properties. In this study, we used MRI to study the phantom and rat liver imaging characteristics of USPIO nanoparticles (<5 nm). The results showed that USPIO nanoparticles (<5 nm) could potentially reduce longitudinal and transverse relaxation times and showed similar relaxation rates compared with commercial gadolinium chelates. In addition, USPIO nanoparticles (<5 nm) demonstrated both positive ( ) and negative ( ) liver contrast enhancement in healthy rats' liver. Furthermore, USPIO nanoparticles showed relatively good in vitro biocompatibility and fast clearance (within 45.17 minutes after intravenous injection) in the normal liver. Taken together, these data might inspire a new personalized and precise diagnostic tool and stimulate new applications for specific targeted molecular probes.
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http://dx.doi.org/10.1155/2019/3687537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679865PMC
July 2020

Baseline perfusion CT parameters as potential biomarkers in predicting long-term prognosis of localized clear cell renal cell carcinoma.

Abdom Radiol (NY) 2019 10;44(10):3370-3376

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Purpose: We aimed to explore the relationship among baseline perfusion CT parameters, clinical, and pathological factors with post-nephrectomy long-term progression-free survival in localized clear cell renal cell carcinoma.

Materials And Methods: This study retrospectively collected 127 patients from March 2005 to May 2007 who undertook perfusion CT. 61 patients were confirmed of pT1N0M0 or pT2N0M0 ccRCC. The mean follow-up time is 118.8 months (± 13.1 m, range 72-135 m). We compared clinical, pathological factors (gender, T stage, age, Fuhrmann grade, VEGF level, and MVD), and perfusion parameters before treatment [blood flow (BF), blood volume, mean transition time, and permeability surface-area product] between groups with post-nephrectomy metastasis and without metastasis. Association between covariates and progression-free survival (PFS) were analyzed using Cox proportional regression.

Results: Among 61 patients, 11 developed distant metastasis (10 in the lung, one in the bone). BF in metastatic group [429.1 (233.8, 570.1) ml/min/100 g] was significantly higher than non-metastatic group [214.3 (153.3, 376.5) ml/min/100 g] (p = 0.011). Metastatic group also had more patients with higher Fuhrmann grade. Multi-covariant Cox regression demonstrated T staging, Fuhrmann grade, and BF were significantly associated with PFS [hazard ratio (HR) 3.35, 3.08, and 1.006]. In another model, BF > 230 ml/min/100 g was associated with PFS (HR 12.90), along with T staging and Fuhrmann grade (HR 4.73, 3.69).

Conclusion: Baseline tumor BF is a potential biomarker in prediction long-term metastasis of localized ccRCC and may help screening for higher risk localized ccRCC patients who need personalized surveillance strategy after nephrectomy.
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http://dx.doi.org/10.1007/s00261-019-02087-zDOI Listing
October 2019

Developing a prediction model based on MRI for pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Abdom Radiol (NY) 2019 09;44(9):2978-2987

Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, #17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.

Purpose: The aim of this study was to build an appropriate diagnostic model for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC), by combining magnetic resonance imaging (MRI) parameters with clinical factors.

Methods: Eighty-four patients with LARC who underwent MR examination before and after nCRT were enrolled in this study. MRI parameters including cylindrical approximated tumor volume (CATV) and relative signal intensity of tumor (rT2wSI) were measured; corresponding reduction rates (RR) were calculated; and MR tumor regression grade (mrTRG) and other conventional MRI parameters were assessed. Logistic regression with lasso regularization was performed and the appropriate prediction model for pCR was built up. An external cohort of thirty-six patients was used as the validation group for testing the model. Receiver-operating characteristic (ROC) analysis was used to assess the diagnostic performance.

Results: In the development and the validation group, 17 patients (20.2%) and 11 patients (30.6%), respectively, achieved pCR. Two CATV-related parameters (CATVpost, which is the CATV measured after nCRT and CATVRR), one rT2wSI-related parameter (rT2wSIRR), and mrTRG were the most important parameters for predicting pCR and were retained in the diagnostic model. In the development group, the area under the receiver-operating characteristic curve (AUC) for predicting pCR is 0.88 [95% confidence interval (CI) 0.78-0.97, p < 0.001], with a sensitivity of 82.4% and a specificity of 83.6%. In the validation group, the AUC is 0.84 (95% CI 0.70-0.98, p = 0.001), with a sensitivity of 81.8% and a specificity of 76.0%.

Conclusion: A diagnostic model including CATVpost, CATVRR, rT2wSIRR, and mrTRG was useful for predicting pCR after nCRT in patients with LARC and may be used as an effective organ-preservation strategy.
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http://dx.doi.org/10.1007/s00261-019-02129-6DOI Listing
September 2019