Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.

BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status. METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n = 128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n = 86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 ( http://keyan.deepwise.com/ ), then radiomics feature extraction was implemented with PyRadiomics library. Recursive feature elimination (RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA). RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p = 0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p = 0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and the DCA verified the benefits of the nomogram. CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.

Prediction Breast Molecular Typing of Invasive Ductal Carcinoma Based on Dynamic Contrast Enhancement Magnetic Resonance Imaging Radiomics Characteristics: A Feasibility Study.

Objective: To investigate the feasibility of radiomics in predicting molecular subtype of breast invasive ductal carcinoma (IDC) based on dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: A total of 303 cases with pathologically confirmed IDC from January 2018 to March 2021 were enrolled in this study, including 223 cases from Fudan University Shanghai Cancer Center (training/test set) and 80 cases from Shaoxing Central Hospital (validation set). All the cases were classified as HR+/Luminal, HER2-enriched, and TNBC according to immunohistochemistry. DCE-MRI original images were treated by semi-automated segmentation to initially extract original and wavelet-transformed radiomic features. The extended logistic regression with least absolute shrinkage and selection operator (LASSO) penalty was applied to identify the optimal radiomic features, which were then used to establish predictive models combined with significant clinical risk factors. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis were adopted to evaluate the effectiveness and clinical benefit of the models established. Results: Of the 223 cases from Fudan University Shanghai Cancer Center, HR+/Luminal cancers were diagnosed in 116 cases (52.02%), HER2-enriched in 71 cases (31.84%), and TNBC in 36 cases (16.14%). Based on the training set, 788 radiomic features were extracted in total and 8 optimal features were further identified, including 2 first-order features, 1 gray-level run length matrix (GLRLM), 4 gray-level co-occurrence matrices (GLCM), and 1 3D shape feature. Three multi-class classification models were constructed by extended logistic regression: clinical model (age, menopause, tumor location, Ki-67, histological grade, and lymph node metastasis), radiomic model, and combined model. The macro-average areas under the ROC curve (macro-AUC) for the three models were 0.71, 0.81, and 0.84 in the training set, 0.73, 0.81, and 0.84 in the test set, and 0.76, 0.82, and 0.83 in the validation set, respectively. Conclusion: The DCE-MRI-based radiomic features are significant biomarkers for distinguishing molecular subtypes of breast cancer noninvasively. Notably, the classification performance could be improved with the fusion analysis of multi-modal features.

Combined model based on enhanced CT texture features in liver metastasis prediction of high-risk gastrointestinal stromal tumors.

PURPOSE: To investigate the use of the combined model based on clinical and enhanced CT texture features for predicting the liver metastasis of high-risk gastrointestinal stromal tumors (GISTs). METHODS: This retrospective study was conducted including 204 patients with pathologically confirmed high-risk GISTs from the Zhejiang Cancer Hospital from January 2015 to June 2021, and 76 cases of them were diagnosed with simultaneous liver metastasis. We randomly divided the cohort into a training cohort (n = 142) and a validation cohort (n = 62) with a ratio of 7:3. All volumes of interest (VOIs) of the high-risk GISTs were manually segmented on the portal venous phase CT images using the ITK-SNAP software. The least absolute shrinkage and selection operator (Lasso) algorithm was performed to determine the most valuable features from a total of 110 texture features extracted by the A-K software to reflect the texture information of the given VOIs. Texture-based predictive model was built from the selected texture features. Independent clinical risk factors were identified through univariate logistic analysis. Then, the texture-based model incorporated the clinical predictors to develop a combined model by multivariate logistic regression. Receiver operating characteristic curve, calibration curve, and decision curve analysis were utilized to analyze the discrimination capacity and clinical application value of the predictive models. RESULTS: The nine optimal texture features were remained after the reduction of dimension using Lasso method. Another four clinical parameters (BMI, location, gastrointestinal bleeding, and CA125 level) were included in the clinical-based predictive model. Finally, with the combination of remaining texture and clinical features, a multivariate logistic regression classifier was built to predict the liver metastasis potential of high-risk GISTs. The remarkable classification performance of the combined model for the prediction of liver metastasis in the subjects with high-risk GISTs was obtained with area under curve (AUC) = 0.919, sensitivity = 83.9%, specificity = 89.7%, and accuracy = 84.9% in our validation group. CONCLUSION: The texture-based radiomic signature derived from the portal venous phase CT images could predict liver metastasis of high-risk GISTs in a non-invasive way. Integrating additional clinical variables into the model further leads to an improvement of liver metastasis risk prediction.

[Digital breast tomosynthesis in diagnosis of dense breast lesions].

OBJECTIVE: To evaluate the value of digital breast tomosynthesis (DBT) in diagnosis of dense breast lesions. METHODS: Clinical and pathological data of 163 patients (58 benign lesions, 122 malignant lesions, and 180 lesions in total) with breast lesions undergoing surgical treatment in Shaoxing Central Hospital from January 2017 to December 2018 were retrospectively analyzed. The lesions were classified into non-homogeneous dense gland type and extremely dense gland type according to BI-RADS creterion. Breast MRI and DBT examinations were performed before the surgery. ROC curve was generated and the diagnostic efficacy of two examination methods for dense breast lesions was evaluated with pathological results as the gold standard. The detection rate, diagnostic accuracy of benign and malignant breast lesions were compared between two methods using chi-square test. The accuracy of lesion size preoperatively evaluated by MRI and DBT was analyzed by Pearson correlation. RESULTS: The detection rate and diagnostic accuracy for benign breast lesions by MRI were higher than those by DBT (91.4% vs. 75.9%, χ2=5.098, P<0.05 and 89.7% vs. 67.2%, χ2=8.617, P<0.01). But there were no significant differences in detection rate and accuracy for malignant lesions by MRI and DBT (98.4% vs. 95.1%, χ2=2.068, P>0.05 and 94.3% vs. 91.8%, χ2=0.569, P>0.05). The areas under the ROC curves of MRI, DBT based on BI-RADS classification were 0.910 and 0.832, respectively (Z=1.860, P>0.05). The sensitivities of MRI, DBT to breast lesions were 93.3% and 86.7%, and the specificities were 68.3% and 79.1%. DBT and MRI measurements were positively correlated with pathological measurements (r=0.887 and 0.949, all P<0.01). CONCLUSIONS: DBT can effectively diagnose benign and malignant breast lesions under dense gland background, and it has similar diagnostic efficacy with MRI for breast malignant lesions.