Development of a machine learning-based radiomics signature for estimating breast cancer TME phenotypes and predicting anti-PD-1/PD-L1 immunotherapy response.

BACKGROUNDS: Since breast cancer patients respond diversely to immunotherapy, there is an urgent need to explore novel biomarkers to precisely predict clinical responses and enhance therapeutic efficacy. The purpose of our present research was to construct and independently validate a biomarker of tumor microenvironment (TME) phenotypes via a machine learning-based radiomics way. The interrelationship between the biomarker, TME phenotypes and recipients' clinical response was also revealed. METHODS: In this retrospective multi-cohort investigation, five separate cohorts of breast cancer patients were recruited to measure breast cancer TME phenotypes via a radiomics signature, which was constructed and validated by integrating RNA-seq data with DCE-MRI images for predicting immunotherapy response. Initially, we constructed TME phenotypes using RNA-seq of 1089 breast cancer patients in the TCGA database. Then, parallel DCE-MRI images and RNA-seq of 94 breast cancer patients obtained from TCIA were applied to develop a radiomics-based TME phenotypes signature using random forest in machine learning. The repeatability of the radiomics signature was then validated in an internal validation set. Two additional independent external validation sets were analyzed to reassess this signature. The Immune phenotype cohort (n = 158) was divided based on CD8 cell infiltration into immune-inflamed and immune-desert phenotypes; these data were utilized to examine the relationship between the immune phenotypes and this signature. Finally, we utilized an Immunotherapy-treated cohort with 77 cases who received anti-PD-1/PD-L1 treatment to evaluate the predictive efficiency of this signature in terms of clinical outcomes. RESULTS: The TME phenotypes of breast cancer were separated into two heterogeneous clusters: Cluster A, an "immune-inflamed" cluster, containing substantial innate and adaptive immune cell infiltration, and Cluster B, an "immune-desert" cluster, with modest TME cell infiltration. We constructed a radiomics signature for the TME phenotypes ([AUC] = 0.855; 95% CI 0.777-0.932; p < 0.05) and verified it in an internal validation set (0.844; 0.606-1; p < 0.05). In the known immune phenotypes cohort, the signature can identify either immune-inflamed or immune-desert tumor (0.814; 0.717-0.911; p < 0.05). In the Immunotherapy-treated cohort, patients with objective response had higher baseline radiomics scores than those with stable or progressing disease (p < 0.05); moreover, the radiomics signature achieved an AUC of 0.784 (0.643-0.926; p < 0.05) for predicting immunotherapy response. CONCLUSIONS: Our imaging biomarker, a practicable radiomics signature, is beneficial for predicting the TME phenotypes and clinical response in anti-PD-1/PD-L1-treated breast cancer patients. It is particularly effective in identifying the "immune-desert" phenotype and may aid in its transformation into an "immune-inflamed" phenotype.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

Predicting the malignancy of extremity soft-tissue tumors by an ultrasound-based radiomics signature.

BACKGROUND: Accurate differentiation of extremity soft-tissue tumors (ESTTs) is important for treatment planning. PURPOSE: To develop and validate an ultrasound (US) image-based radiomics signature to predict ESTTs malignancy. MATERIAL AND METHODS: A dataset of US images from 108 ESTTs were retrospectively enrolled and divided into the training cohort (78 ESTTs) and validation cohort (30 ESTTs). A total of 1037 radiomics features were extracted from each US image. The most useful predictive radiomics features were selected by the maximum relevance and minimum redundancy method, least absolute shrinkage, and selection operator algorithm in the training cohort. A US-based radiomics signature was built based on these selected radiomics features. In addition, a conventional radiologic model based on the US features from the interpretation of two experienced radiologists was developed by a multivariate logistic regression algorithm. The diagnostic performances of the selected radiomics features, the US-based radiomics signature, and the conventional radiologic model for differentiating ESTTs were evaluated and compared in the validation cohort. RESULTS: In the validation cohort, the area under the curve (AUC), sensitivity, and specificity of the US-based radiomics signature for predicting ESTTs malignancy were 0.866, 84.2%, and 81.8%, respectively. The US-based radiomics signature had better diagnostic predictability for predicting ESTT malignancy than the best single radiomics feature and the conventional radiologic model (AUC = 0.866 vs. 0.719 vs. 0.681 for the validation cohort, all P <0.05). CONCLUSION: The US-based radiomics signature could provide a potential imaging biomarker to accurately predict ESTT malignancy.

A nomogram based on CT texture features to predict the response of patients with advanced pancreatic cancer treated with chemotherapy.

OBJECTIVE: This study aimed to evaluate the predictive value of computed tomography (CT) texture features in the treatment response of patients with advanced pancreatic cancer (APC) receiving palliative chemotherapy. METHODS: This study enrolled 84 patients with APC treated with first-line chemotherapy and conducted texture analysis on primary pancreatic tumors. 59 patients and 25 were randomly assigned to the training and validation cohorts at a ratio of 7:3. The treatment response to chemotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1). The patients were divided into progressive and non-progressive groups. The least absolute shrinkage selection operator (LASSO) was applied for feature selection in the training cohort and a radiomics signature (RS) was calculated. A nomogram was developed based on a multivariate logistic regression model incorporating the RS and carbohydrate antigen 19-9 (CA19-9), and was internally validated using the C-index and calibration plot. We performed the decision curve analysis (DCA) and clinical impact curve analysis to reflect the clinical utility of the nomogram. The nomogram was further externally confirmed in the validation cohort. RESULTS: The multivariate logistic regression analysis indicated that the RS and CA19-9 were independent predictors (P < 0.05), and a trend was found for chemotherapy between progressive and non-progressive groups. The nomogram incorporating RS, CA19-9 and chemotherapy showed favorable discriminative ability in the training (C-index = 0.802) and validation (C-index = 0.920) cohorts. The nomogram demonstrated favorable clinical utility. CONCLUSION: The RS of significant texture features was significantly associated with the early treatment effect of patients with APC treated with chemotherapy. Based on the RS, CA19-9 and chemotherapy, the nomogram provided a promising way to predict chemotherapeutic effects for APC patients.

Preoperative prediction of extrathyroidal extension: radiomics signature based on multimodal ultrasound to papillary thyroid carcinoma.

BACKGROUND: There is a recognized need for additional approaches to improve the accuracy of extrathyroidal extension (ETE) diagnosis in papillary thyroid carcinoma (PTC) before surgery. Up to now, multimodal ultrasound has been widely applied in disease diagnosis. We investigated the value of radiomic features extracted from multimodal ultrasound in the preoperative prediction of ETE. METHODS: We retrospectively pathologically confirmed PTC lesions in 235 patients from January 2019 to April 2022 in our hospital, including 45 ETE lesions and 205 non-ETE lesions. MaZda software was employed to obtain radiomics parameters in multimodal sonography. The most valuable radiomics features were selected by the Fisher coefficient, mutual information, probability of classification error and average correlation coefficient methods (F + MI + PA) in combination with the least absolute shrinkage and selection operator (LASSO) method. Finally, the multimodal model was developed by incorporating the clinical records and radiomics features through fivefold cross-validation with a linear support vector machine algorithm. The predictive performance was evaluated by sensitivity, specificity, accuracy, F1 scores and the area under the receiver operating characteristic curve (AUC) in the training and test sets. RESULTS: A total of 5972 radiomics features were extracted from multimodal sonography, and the 13 most valuable radiomics features were selected from the training set using the F + MI + PA method combined with LASSO regression. The multimodal prediction model yielded AUCs of 0.911 (95% CI 0.866-0.957) and 0.716 (95% CI 0.522-0.910) in the cross-validation and test sets, respectively. The multimodal model and radiomics model showed good discrimination between ETE and non-ETE lesions. CONCLUSION: Radiomics features based on multimodal ultrasonography could play a promising role in detecting ETE before surgery.

Prediction of Mild Cognitive Impairment Progression to Alzheimer's Disease Based on Diffusion Tensor Imaging-Derived Diffusion Parameters: Construction and Validation of a Nomogram.

INTRODUCTION: The aim of the study was to construct and validate a nomogram that combines diffusion tensor imaging (DTI) parameters and clinically relevant features for predicting the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHOD: A retrospective analysis was conducted on the MRI and clinical data of 121 MCI patients, of whom 32 progressed to AD during a 4-year follow-up period. The MCI patients were divided into training and validation sets at a ratio of 7:3. DTI features were extracted from MCI patient data in the training set, and their dimensionality was reduced to construct a radiomics signature (RS). Then, combining the RS with independent predictors of MCI disease progression, a joint model was constructed, and a nomogram was generated. Finally, the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the diagnostic and clinical efficacy of the nomogram based on the data from the validation set. RESULT: The AUCs of the RS in the training and validation sets were 0.81 and 0.84, with sensitivities of 0.87 and 0.78 and specificities of 0.71 and 0.81, respectively. Multiple logistic regression analysis showed that the RS, clinical dementia rating scale score, and Alzheimer's disease assessment scale score were the independent predictors of progression and were thus used to construct the nomogram. The AUCs of the nomogram in the training and validation sets were 0.89 and 0.91, respectively, with sensitivities of 0.78 and 0.89 and specificities of 0.90 and 0.88, respectively. DCA showed that the nomogram was the most valuable model for predicting the progression of MCI to AD and that it provided greater net benefits than other analysed models. CONCLUSION: Changes in white matter fibre bundles can serve as predictive imaging markers for MCI disease progression, and the combination of white matter DTI features and relevant clinical features can be used to construct a nomogram with important predictive value for MCI disease progression.

Development and Validation of CT-Based Radiomics Signature for Overall Survival Prediction in Multi-organ Cancer.

The malignant tumors in nature share some common morphological characteristics. Radiomics is not only images but also data; we think that a probability exists in a set of radiomics signatures extracted from CT scan images of one cancer tumor in one specific organ also be utilized for overall survival prediction in different types of cancers in different organs. The retrospective study enrolled four data sets of cancer patients in three different organs (420, 157, 137, and 191 patients for lung 1 training, lung 2 testing, and two external validation set: kidney and head and neck, respectively). In the training set, radiomics features were obtained from CT scan images, and essential features were chosen by LASSO algorithm. Univariable and multivariable analyses were then conducted to find a radiomics signature via Cox proportional hazard regression. The Kaplan-Meier curve was performed based on the risk score. The integrated time-dependent area under the ROC curve (iAUC) was calculated for each predictive model. In the training set, Kaplan-Meier curve classified patients as high or low-risk groups (p-value < 0.001; log-rank test). The risk score of radiomics signature was locked and independently evaluated in the testing set, and two external validation sets showed significant differences (p-value < 0.05; log-rank test). A combined model (radiomics + clinical) showed improved iAUC in lung 1, lung 2, head and neck, and kidney data set are 0.621 (95% CI 0.588, 0.654), 0.736 (95% CI 0.654, 0.819), 0.732 (95% CI 0.655, 0.809), and 0.834 (95% CI 0.722, 0.946), respectively. We believe that CT-based radiomics signatures for predicting overall survival in various cancer sites may exist.

Evaluating Tumor-Infiltrating Lymphocytes in Breast Cancer Using Preoperative MRI-Based Radiomics.

BACKGROUND: Evaluating tumor-infiltrating lymphocytes (TILs) in patients with breast cancer using radiomics has been rarely explored. PURPOSE: To establish a radiomics nomogram based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for preoperatively evaluating TIL level. STUDY TYPE: Retrospective. POPULATION: A total of 154 patients with breast cancer were divided into a training cohort (N = 87) and a test cohort (N = 67), who were further divided into low TIL (<50%) and high TIL (≥50%) subgroups according to the histopathological results. FIELD STRENGTH/SEQUENCE: 3.0 T; axial T2-weighted imaging (fast spin echo), diffusion-weighted imaging (spin echo-echo planar imaging), and the volume imaging for breast assessment DCE sequence (gradient recalled echo). ASSESSMENT: A radiomics signature was developed from the training dataset and independent risk factors were selected by multivariate logistic regression to build a clinical model. A nomogram model was built by combining radiomics score and risk factors. The performance of the nomogram was assessed using calibration curves and decision curves. The area under the receiver operating characteristic (ROC) curve, accuracy, sensitivity, and specificity were calculated. STATISTICAL TESTS: The least absolute shrinkage and selection operator, univariate and multivariate logistic regression analysis, t-tests and chi-squared tests or Fisher's exact test, Hosmer-Lemeshow test, ROC analysis, and decision curve analysis were conducted. P < 0.05 was considered statistically significant. RESULTS: The radiomics signature and nomogram model exhibited better calibration and validation performance in the training (radiomics: area under the curve [AUC] 0.86; nomogram: AUC 0.88) and test (radiomics: AUC 0.83; nomogram: AUC 0.84) datasets compared with clinical model (training: AUC 0.76; test: AUC 0.72). The decision curve demonstrated that the nomogram model exhibited better performance than the clinical model, with a threshold probability between 0.15 and 0.9. DATA CONCLUSION: The nomogram model based on preoperative MRI exhibited an excellent ability for the noninvasive evaluation of TILs in breast cancer. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Predicting the progression of Parkinson's disease using conventional MRI and machine learning: An application of radiomic biomarkers in whole-brain white matter.

PURPOSE: This study aimed to develop and validate a radiomics model based on whole-brain white matter and clinical features to predict the progression of Parkinson disease (PD). METHODS: PD patient data from the Parkinson's Progress Markers Initiative (PPMI) database was evaluated. Seventy-two PD patients with disease progression, as measured by the Hoehn-Yahr Scale (HYS) (stage 1-5), and 72 PD patients with stable PD were matched by sex, age, and category of HYS and included in the current study. Each individual's T1 -weighted MRI scans at the baseline timepoint were segmented to isolate whole-brain white matter for radiomics feature extraction. The total dataset was divided into a training and test set according to subject serial number. The size of the training dataset was reduced using the maximum relevance minimum redundancy (mRMR) algorithm to construct a radiomics signature using machine learning. Finally, a joint model was constructed by incorporating the radiomics signature and clinical progression scores. The test data were then used to validate the prediction models, which were evaluated based on discrimination, calibration, and clinical utility. RESULTS: Based on the overall data, the areas under curve (AUCs) of the joint model, signature and Unified Parkinson Disease Rating Scale III PD rating score were 0.836, 0.795, and 0.550, respectively. Furthermore, the sensitivities were 0.805, 0.875, and 0.292, respectively, and the specificities were 0.722, 0.697, and 0.861, respectively. In addition, the predictive accuracy of the model was 0.827, the sensitivity was 0.829 and the specificity was 0.702 for stage-1 PD. For stage-2 PD, the predictive accuracy of the model was 0.854, the sensitivity was 0.960, and the specificity was 0.600. CONCLUSION: Our results provide evidence that conventional structural MRI can predict the progression of PD. This work also supports the use of a simple radiomics signature built from whole-brain white matter features as a useful tool for the assessment and monitoring of PD progression.

Distinguishing cardiac myxomas from cardiac thrombi by a radiomics signature based on cardiovascular contrast-enhanced computed tomography images.

BACKGROUND: Cardiac myxomas (CMs) and thrombi are associated with high morbidity and mortality. These two conditions need totally different treatments. However, they are difficult to distinguish using naked eye. In clinical, misdiagnoses occur now and then. This study aimed to compare the characteristics of CMs and cardiac thrombi and investigate the value of a radiomics signature in distinguishing CMs from cardiac thrombi, based on cardiovascular contrast-enhanced computed tomography (CECT) images. METHODS: A total of 109 patients who had CMs (n = 59) and cardiac thrombi (n = 50) were enrolled in this retrospective study from 2009 to 2019. First, the lesion characteristics of cardiovascular CECT images were documented and compared by two radiologists. Then all patients were randomly allotted to either a primary group or a validation group according to a 7:3 ratio. Univariate analysis and the least absolute shrinkage and selection operator were used to select robust features. The best radiomics signature was constructed and validated using multivariate logistic regression. An independent clinical model was created for comparison. RESULTS: The best radiomics signature was developed using eight selected radiomics. The classification accuracies of the radiomics signature were 90.8% and 90.9%, and the area under the receiver operating characteristic curves were 0.969 and 0.926 in the training and testing cohorts, respectively. Cardiovascular CECT images showed that the two diseases had significant differences in location, surface, Hydrothorax, pericardial effusion and heart enlargement. The naked eye findings were used to create the clinical model. All metrics of the radiomics signature were higher than those of clinical model. CONCLUSIONS: Compared with clinical model, the radiomics signature based on cardiovascular CECT performed better in differentiating CMs and thrombi, suggesting that it could help improving the diagnostic efficiency.

A radiomics signature to identify malignant and benign liver tumors on plain CT images.

BACKGROUND: In regular examinations, it may be difficult to visually identify benign and malignant liver tumors based on plain computed tomography (CT) images. RCAD (radiomics-based computer-aided diagnosis) has proven to be helpful and provide interpretability in clinical use. OBJECTIVE: This work aims to develop a CT-based radiomics signature and investigate its correlation with malignant/benign liver tumors. METHODS: We retrospectively analyzed 168 patients of hepatocellular carcinoma (malignant) and 117 patients of hepatic hemangioma (benign). Texture features were extracted from plain CT images and used as candidate features. A radiomics signature was developed from the candidate features. We performed logistic regression analysis and used a multiple-regression coefficient (termed as R) to assess the correlation between the developed radiomics signature and malignant/benign liver tumors. Finally, we built a logistic regression model to classify benign and malignant liver tumors. RESULTS: Thirteen features were chosen from 1223 candidate features to constitute the radiomics signature. The logistic regression analysis achieved an R = 0.6745, which was much larger than Rα = 0.3703 (the critical value of R at significant level α = 0.001). The logistic regression model achieved an average AUC of 0.87. CONCLUSIONS: The developed radiomics signature was statistically significantly correlated with malignant/benign liver tumors (p < 0.001). It has potential to help enhance physicians' diagnostic abilities and play an important role in RCADs.

Radiomics signature for dynamic changes of tumor-infiltrating CD8+ T cells and macrophages in cervical cancer during chemoradiotherapy.

BACKGROUND: Our previous study suggests that tumor CD8+ T cells and macrophages (defined as CD68+ cells) infiltration underwent dynamic and heterogeneous changes during concurrent chemoradiotherapy (CCRT) in cervical cancer patients, which correlated with their short-term tumor response. This study aims to develop a CT image-based radiomics signature for such dynamic changes. METHODS: Thirty cervical squamous cell carcinoma patients, who were treated with CCRT followed by brachytherapy, were included in this study. Pre-therapeutic CT images were acquired. And tumor biopsies with immunohistochemistry at primary sites were performed at baseline (0 fraction (F)) and immediately after 10F. Radiomics features were extracted from the region of interest (ROI) of CT images using Matlab. The LASSO regression model with ten-fold cross-validation was utilized to select features and construct an immunomarker classifier and a radiomics signature. Their performance was evaluated by the area under the curve (AUC). RESULTS: The changes of tumor-infiltrating CD8+T cells and macrophages after 10F radiotherapy as compared to those at baseline were used to generate the immunomarker classifier (AUC= 0.842, 95% CI:0.680-1.000). Additionally, a radiomics signature was developed using 4 key radiomics features to predict the immunomarker classifier (AUC=0.875, 95% CI:0.753-0.997). The patients stratified based on this signature exhibited significant differences in treatment response (p = 0.004). CONCLUSION: The radiomics signature could be used as a potential predictor for the CCRT-induced dynamic alterations of CD8+ T cells and macrophages, which may provide a less invasive approach to appraise tumor immune status during CCRT in cervical cancer compared to tissue biopsy.

Integration of Radiomics and Immune-Related Genes Signatures for Predicting Axillary Lymph Node Metastasis in Breast Cancer.

BACKGROUND: To develop a radiogenomics nomogram for predicting axillary lymph node (ALN) metastasis in breast cancer and reveal underlying associations between radiomics features and biological pathways. MATERIALS AND METHODS: This study included 1062 breast cancer patients, 90 patients with both DCE-MRI and gene expression data. The optimal immune-related genes and radiomics features associated with ALN metastasis were firstly calculated, and corresponding feature signatures were constructed to further validate their performances in predicting ALN metastasis. The radiogenomics nomogram for predicting the risk of ALN metastasis was established by integrating radiomics signature, immune-related genes (IRG) signature, and critical clinicopathological factors. Gene modules associated with key radiomics features were identified by weighted gene co-expression network analysis (WGCNA) and submitted to functional enrichment analysis. Gene set variation analysis (GSVA) and correlation analysis were performed to investigate the associations between radiomics features and biological pathways. RESULTS: The radiogenomics nomogram showed promising predictive power for predicting ALN metastasis, with AUCs of 0.973 and 0.928 in the training and testing groups, respectively. WGCNA and functional enrichment analysis revealed that gene modules associated with key radiomics features were mainly enriched in breast cancer metastasis-related pathways, such as focal adhesion, ECM-receptor interaction, and cell adhesion molecules. GSVA also identified pathway activities associated with radiomics features such as glycogen synthesis, integration of energy metabolism. CONCLUSION: The radiogenomics nomogram can serve as an effective tool to predict the risk of ALN metastasis. This study provides further evidence that radiomics phenotypes may be driven by biological pathways related to breast cancer metastasis.

Computed tomography-based radiomics prediction of CTLA4 expression and prognosis in clear cell renal cell carcinoma.

OBJECTIVES: To predict CTLA4 expression levels and prognosis of clear cell renal cell carcinoma (ccRCC) by constructing a computed tomography-based radiomics model and establishing a nomogram using clinicopathologic factors. METHODS: The clinicopathologic parameters and genomic data were extracted from 493 ccRCC cases of the Cancer Genome Atlas (TCGA)-KIRC database. Univariate and multivariate Cox regression and Kaplan-Meier analysis were performed for prognosis analysis. Cibersortx was applied to evaluate the immune cell composition. Radiomic features were extracted from the TCGA/the Cancer Imaging Archive (TCIA) (n = 102) datasets. The support vector machine (SVM) was employed to establish the radiomics signature for predicting CTLA4 expression. Receiver operating characteristic curve (ROC), decision curve analysis (DCA), and precision-recall curve were utilized to assess the predictive performance of the radiomics signature. Correlations between radiomics score (RS) and selected features were also evaluated. An RS-based nomogram was constructed to predict prognosis. RESULTS: CTLA4 was significantly overexpressed in ccRCC tissues and was related to lower overall survival. A higher CTLA4 expression was independently linked to the poor prognosis (HR = 1.458, 95% CI 1.13-1.881, p = 0.004). The radiomics model for the prediction of CTLA4 expression levels (AUC = 0.769 in the training set, AUC = 0.724 in the validation set) was established using seven radiomic features. A significant elevation in infiltrating M2 macrophages was observed in the RS high group (p < 0.001). The predictive efficiencies of the RS-based nomogram measured by AUC were 0.826 at 12 months, 0.805 at 36 months, and 0.76 at 60 months. CONCLUSIONS: CTLA4 mRNA expression status in ccRCC could be predicted noninvasively using a radiomics model based on nephrographic phase contrast-enhanced CT images. The nomogram established by combining RS and clinicopathologic factors could predict overall survival for ccRCC patients. Our findings may help stratify prognosis of ccRCC patients and identify those who may respond best to ICI-based treatments.

A transfer learning approach on MRI-based radiomics signature for overall survival prediction of low-grade and high-grade gliomas.

Lower-grade gliomas (LGG) can eventually progress to glioblastoma (GBM) and death. In the context of the transfer learning approach, we aimed to train and test an MRI-based radiomics model for predicting survival in GBM patients and validate it in LGG patients. From each patient's 704 MRI-based radiomics features, we chose seventeen optimal radiomics signatures in the GBM training set (n = 71) and used these features in both the GBM testing set (n = 31) and LGG validation set (n = 107) for further analysis. Each patient's risk score, calculated based on those optimal radiomics signatures, was chosen to represent the radiomics model. We compared the radiomics model with clinical, gene status models, and combined model integrating radiomics, clinical, and gene status in predicting survival. The average iAUCs of combined models in training, testing, and validation sets were respectively 0.804, 0.878, and 0.802, and those of radiomics models were 0.798, 0.867, and 0.717. The average iAUCs of gene status and clinical models ranged from 0.522 to 0.735 in all three sets. The radiomics model trained in GBM patients can effectively predict the overall survival of GBM and LGG patients, and the combined model improved this ability.

Application of DCE-MRI radiomics signature analysis in differentiating molecular subtypes of luminal and non-luminal breast cancer.

Background: The goal of this study was to develop and validate a radiomics signature based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) preoperatively differentiating luminal and non-luminal molecular subtypes in patients with invasive breast cancer. Methods: One hundred and thirty-five invasive breast cancer patients with luminal (n = 78) and non-luminal (n = 57) molecular subtypes were divided into training set (n = 95) and testing set (n = 40) in a 7:3 ratio. Demographics and MRI radiological features were used to construct clinical risk factors. Radiomics signature was constructed by extracting radiomics features from the second phase of DCE-MRI images and radiomics score (rad-score) was calculated. Finally, the prediction performance was evaluated in terms of calibration, discrimination, and clinical usefulness. Results: Multivariate logistic regression analysis showed that no clinical risk factors were independent predictors of luminal and non-luminal molecular subtypes in invasive breast cancer patients. Meanwhile, the radiomics signature showed good discrimination in the training set (AUC, 0.86; 95% CI, 0.78-0.93) and the testing set (AUC, 0.80; 95% CI, 0.65-0.95). Conclusion: The DCE-MRI radiomics signature is a promising tool to discrimination luminal and non-luminal molecular subtypes in invasive breast cancer patients preoperatively and noninvasively.

Ultrasound radiomics based on axillary lymph nodes images for predicting lymph node metastasis in breast cancer.

Objectives: To determine whether ultrasound radiomics can be used to distinguish axillary lymph nodes (ALN) metastases in breast cancer based on ALN imaging. Methods: A total of 147 breast cancer patients with 41 non-metastatic lymph nodes and 109 metastatic lymph nodes were divided into a training set (105 ALN) and a validation set (45 ALN). Radiomics features were extracted from ultrasound images and a radiomics signature (RS) was built. The Intraclass correlation coefficients (ICCs), Spearman correlation analysis, and least absolute shrinkage and selection operator (LASSO) methods were used to select the ALN status-related features. All images were assessed by two radiologists with at least 10 years of experience in ALN ultrasound examination. The performance levels of the model and radiologists in the training and validation subgroups were then evaluated and compared. Result: Radiomics signature accurately predicted the ALN status, achieved an area under the receiver operator characteristic curve of 0.929 (95%CI, 0.881-0.978) and area under curve(AUC) of 0.919 (95%CI, 95%CI, 0.841-0.997) in training and validation cohorts respectively. The radiomics model performed better than two experts' prediction of ALN status in both cohorts (P<0.05). Besides, prediction in subgroups based on baseline clinicopathological information also achieved good discrimination performance, with an AUC of 0.937, 0.918, 0.885, 0.930, and 0.913 in HR+/HER2-, HER2+, triple-negative, tumor sized ≤ 3cm and tumor sized>3 cm, respectively. Conclusion: The radiomics model demonstrated a good ability to predict ALN status in patients with breast cancer, which might provide essential information for decision-making.

18F-FDG PET/CT radiomics signature and clinical parameters predict progression-free survival in breast cancer patients: A preliminary study.

Introduction: This study aimed to investigate the feasibility of predicting progression-free survival (PFS) in breast cancer patients using pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) radiomics signature and clinical parameters. Methods: Breast cancer patients who underwent 18F-FDG PET/CT imaging before treatment from January 2012 to December 2020 were eligible for study inclusion. Eighty-seven patients were randomly divided into training (n = 61) and internal test sets (n = 26) and an additional 25 patients were used as the external validation set. Clinical parameters, including age, tumor size, molecular subtype, clinical TNM stage, and laboratory findings were collected. Radiomics features were extracted from preoperative PET/CT images. Least absolute shrinkage and selection operators were applied to shrink feature size and build a predictive radiomics signature. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier analysis were used to assess the association of rad-score and clinical parameter with PFS. Nomograms were constructed to visualize survival prediction. C-index and calibration curve were used to evaluate nomogram performance. Results: Eleven radiomics features were selected to generate rad-score. The clinical model comprised three parameters: clinical M stage, CA125, and pathological N stage. Rad-score and clinical-model were significantly associated with PFS in the training set (P< 0.01) but not the test set. The integrated clinical-radiomics (ICR) model was significantly associated with PFS in both the training and test sets (P< 0.01). The ICR model nomogram had a significantly higher C-index than the clinical model and rad-score in the training and test sets. The C-index of the ICR model in the external validation set was 0.754 (95% confidence interval, 0.726-0.812). PFS significantly differed between the low- and high-risk groups stratified by the nomogram (P = 0.009). The calibration curve indicated the ICR model provided the greatest clinical benefit. Conclusion: The ICR model, which combined clinical parameters and preoperative 18F-FDG PET/CT imaging, was able to independently predict PFS in breast cancer patients and was superior to the clinical model alone and rad-score alone.

Radiomics Signature Based on Support Vector Machines for the Prediction of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

The objective of this study was to evaluate the discriminative capabilities of radiomics signatures derived from three distinct machine learning algorithms and to identify a robust radiomics signature capable of predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy in patients diagnosed with locally advanced rectal cancer (LARC). In a retrospective study, 211 LARC patients were consecutively enrolled and divided into a training cohort (n = 148) and a validation cohort (n = 63). From pretreatment contrast-enhanced planning CT images, a total of 851 radiomics features were extracted. Feature selection and radiomics score (Radscore) construction were performed using three different machine learning methods: least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine (SVM). The SVM-derived Radscore demonstrated a strong correlation with the pCR status, yielding area under the receiver operating characteristic curves (AUCs) of 0.880 and 0.830 in the training and validation cohorts, respectively, outperforming the RF and LASSO methods. Based on this, a nomogram was developed by combining the SVM-based Radscore with clinical indicators to predict pCR after neoadjuvant chemoradiotherapy. The nomogram exhibited superior predictive power, achieving AUCs of 0.910 and 0.866 in the training and validation cohorts, respectively. Calibration curves and decision curve analyses confirmed its appropriateness. The SVM-based Radscore demonstrated promising performance in predicting pCR for LARC patients. The machine learning-driven nomogram, which integrates the Radscore and clinical indicators, represents a valuable tool for predicting pCR in LARC patients.

Combined Radiomics-Clinical Model to Predict Radiotherapy Response in Inoperable Stage III and IV Non-Small-Cell Lung Cancer.

Purpose: Radiotherapy is a promising treatment option for lung cancer, but patients' responses vary. The purpose of the study was to investigate the potential of radiomics and clinical signature for predicting the radiotherapy sensitivity and overall survival of inoperable stage III and IV non-small-cell lung cancer (NSCLC) patients. Materials: This retrospective study collected 104 inoperable stage III and IV NSCLC patients at the Yunnan Cancer Hospital from October 2016 to September 2020. They were divided into radiation-sensitive and non-sensitive groups. We used analysis of variance (ANOVA) to select features and support vector machine (SVM) to build the radiomic model. Furthermore, the logistic regression method was used to screen out clinically relevant predictive factors and construct the combined model of radiomics-clinical features. Finally, survival was estimated using the Kaplan-Meier method. Results: There were 40 patients in the radiation-sensitive group and 64 in the non-sensitive group. These patients were divided into training set (73 cases) and testing set (31 cases) according to the ratio of 7:3. Nine radiomics features and one clinical feature were significantly associated with radiotherapy sensitivity. Both the radiomics model and combined model have good predictive performance (the areas under the curve (AUC) values of the testing set were 0.864 (95% confidence interval [CI]: 0.683-0.996) and 0.868 (95% CI: 0.689-1.000), respectively). Only platelet level status was associated with overall survival. Conclusion: The combined model constructed based on radiomics and clinical features can effectively identify the radiation-sensitive population and provide valuable clinical information. Patients with higher platelet levels may have a poor prognosis.