Development and validation of a clinical decision support system based on PSA, microRNAs, and MRI for the detection of prostate cancer.

OBJECTIVES: The aims of this study are to develop and validate a clinical decision support system based on demographics, prostate-specific antigen (PSA), microRNA (miRNA), and MRI for the detection of prostate cancer (PCa) and clinical significant (cs) PCa, and to assess if this system performs better compared to MRI alone. METHODS: This retrospective, multicenter, observational study included 222 patients (mean age 66, range 46-75 years) who underwent prostate MRI, miRNA (let-7a-5p and miR-103a-3p) assessment, and biopsy. Monoparametric and multiparametric models including age, PSA, miRNA, and MRI outcome were trained on 65% of the data and then validated on the remaining 35% to predict both PCa (any Gleason grade [GG]) and csPCa (GG ≥ 2 vs GG = 1/negative). Accuracy, sensitivity, specificity, positive and negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated. RESULTS: MRI outcome was the best predictor in the monoparametric model for both detection of PCa, with sensitivity of 90% (95%CI 73-98%) and NPV of 93% (95%CI 82-98%), and for csPCa identification, with sensitivity of 91% (95%CI 72-99%) and NPV of 95% (95%CI 84-99%). Sensitivity and NPV of PSA + miRNA for the detection of csPCa were not statistically different from the other models including MRI alone. CONCLUSION: MRI stand-alone yielded the best prediction models for both PCa and csPCa detection in biopsy-naïve patients. The use of miRNAs let-7a-5p and miR-103a-3p did not improve classification performances compared to MRI stand-alone results. CLINICAL RELEVANCE STATEMENT: The use of miRNA (let-7a-5p and miR-103a-3p), PSA, and MRI in a clinical decision support system (CDSS) does not improve MRI stand-alone performance in the detection of PCa and csPCa. KEY POINTS: • Clinical decision support systems including MRI improve the detection of both prostate cancer and clinically significant prostate cancer with respect to PSA test and/or microRNA. • The use of miRNAs let-7a-5p and miR-103a-3p did not significantly improve MRI stand-alone performance. • Results of this study were in line with previous works on MRI and microRNA.

Development and Validation of an Explainable Radiomics Model to Predict High-Aggressive Prostate Cancer: A Multicenter Radiomics Study Based on Biparametric MRI.

In the last years, several studies demonstrated that low-aggressive (Grade Group (GG) ≤ 2) and high-aggressive (GG ≥ 3) prostate cancers (PCas) have different prognoses and mortality. Therefore, the aim of this study was to develop and externally validate a radiomic model to noninvasively classify low-aggressive and high-aggressive PCas based on biparametric magnetic resonance imaging (bpMRI). To this end, 283 patients were retrospectively enrolled from four centers. Features were extracted from apparent diffusion coefficient (ADC) maps and T2-weighted (T2w) sequences. A cross-validation (CV) strategy was adopted to assess the robustness of several classifiers using two out of the four centers. Then, the best classifier was externally validated using the other two centers. An explanation for the final radiomics signature was provided through Shapley additive explanation (SHAP) values and partial dependence plots (PDP). The best combination was a naïve Bayes classifier trained with ten features that reached promising results, i.e., an area under the receiver operating characteristic (ROC) curve (AUC) of 0.75 and 0.73 in the construction and external validation set, respectively. The findings of our work suggest that our radiomics model could help distinguish between low- and high-aggressive PCa. This noninvasive approach, if further validated and integrated into a clinical decision support system able to automatically detect PCa, could help clinicians managing men with suspicion of PCa.

Virtual biopsy in abdominal pathology: where do we stand?

In recent years, researchers have explored new ways to obtain information from pathological tissues, also exploring non-invasive techniques, such as virtual biopsy (VB). VB can be defined as a test that provides promising outcomes compared to traditional biopsy by extracting quantitative information from radiological images not accessible through traditional visual inspection. Data are processed in such a way that they can be correlated with the patient's phenotypic expression, or with molecular patterns and mutations, creating a bridge between traditional radiology, pathology, genomics, and artificial intelligence (AI). Radiomics is the backbone of VB, since it allows the extraction and selection of features from radiological images, feeding them into AI models in order to derive lesions' pathological characteristics and molecular status. Presently, the output of VB provides only a gross approximation of the findings of tissue biopsy. However, in the future, with the improvement of imaging resolution and processing techniques, VB could partially substitute the classical surgical or percutaneous biopsy, with the advantage of being non-invasive, comprehensive, accounting for lesion heterogeneity, and low cost. In this review, we investigate the concept of VB in abdominal pathology, focusing on its pipeline development and potential benefits.

Delta-Radiomics Predicts Response to First-Line Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients with Liver Metastases.

The purpose of this paper is to develop and validate a delta-radiomics score to predict the response of individual colorectal cancer liver metastases (lmCRC) to first-line FOLFOX chemotherapy. Three hundred one lmCRC were manually segmented on both CT performed at baseline and after the first cycle of first-line FOLFOX, and 107 radiomics features were computed by subtracting textural features of CT at baseline from those at timepoint 1 (TP1). LmCRC were classified as nonresponders (R-) if they showed progression of disease (PD), according to RECIST1.1, before 8 months, and as responders (R+), otherwise. After feature selection, we developed a decision tree statistical model trained using all lmCRC coming from one hospital. The final output was a delta-radiomics signature subsequently validated on an external dataset. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values in correctly classifying individual lesions were assessed on both datasets. Per-lesion sensitivity, specificity, PPV, and NPV were 99%, 94%, 95%, 99%, 85%, 92%, 90%, and 87%, respectively, in the training and validation datasets. The delta-radiomics signature was able to reliably predict R- lmCRC, which were wrongly classified by lesion RECIST as R+ at TP1, (93%, averaging training and validation set, versus 67% of RECIST). The delta-radiomics signature developed in this study can reliably predict the response of individual lmCRC to oxaliplatin-based chemotherapy. Lesions forecasted as poor or nonresponders by the signature could be further investigated, potentially paving the way to lesion-specific therapies.

Comparison of radiomics approaches to predict resistance to 1st line chemotherapy in liver metastatic colorectal cancer.

Colorectal cancer (CRC) has the second-highest tumor incidence and is a leading cause of death by cancer. Nearly 20% of patients with CRC will have metastases (mts) at the time of diagnosis, and more than 50% of patients with CRC develop metastases during their disease. Unfortunately, only 45% of patients after a chemotherapy will respond to treatment. The aim of this study is to develop and validate a machine learning algorithm to predict response of individual liver mts, using CT scans. Understanding which mts will respond or not will help clinicians in providing a more efficient per-lesion treatment based on patient specific response and not only following a standard treatment. A group of 92 patients was enrolled from two Italian institutions. CT scans were collected, and the portal venous phase was manually segmented by an expert radiologist. Then, 75 radiomics features were extracted both from 7x7 ROIs that moved across the image and from the whole 3D mts. Feature selection was performed using a genetic algorithm. Results are presented as a comparison of the two different approaches of features extraction and different classification algorithms. Accuracy (ACC), sensitivity (SE), specificity (SP), negative and positive predictive values (NPV and PPV) were evaluated for all lesions (per-lesion analysis) and patients (per-patient analysis) in the construction and validation sets. Best results were obtained in the per-lesion analysis from the 3D approach using a Support Vector Machine as classifier. We reached on the training set an ACC of 81%, while on test set, we obtained SE of 76%, SP of 67%, PPV of 69% and NPV of 75%. On the validation set a SE of 61%, SP of 60%, PPV of 57% and NPV of 64% were reached. The promising results obtained in the validation dataset should be extended to a larger cohort of patient to further validate our method.Clinical Relevance- to develop a radiomics signatures predicting single liver mts response to therapy. A personalized mts approach is important to avoid unnecessary toxicity offering more suitable treatments and a better quality of life to oncological patients.

Deep learning model for automatic prostate segmentation on bicentric T2w images with and without endorectal coil.

Automatic segmentation of the prostate on Magnetic Resonance Imaging (MRI) is one of the topics on which research has focused in recent years as it is a fundamental first step in the building process of a Computer aided diagnosis (CAD) system for cancer detection. Unfortunately, MRI acquired in different centers with different scanners leads to images with different characteristics. In this work, we propose an automatic algorithm for prostate segmentation, based on a U-Net applying transfer learning method in a bi-center setting. First, T2w images with and without endorectal coil from 80 patients acquired at Center A were used as training set and internal validation set. Then, T2w images without endorectal coil from 20 patients acquired at Center B were used as external validation. The reference standard for this study was manual segmentation of the prostate gland performed by an expert operator. The results showed a Dice similarity coefficient >85% in both internal and external validation datasets.Clinical Relevance- This segmentation algorithm could be integrated into a CAD system to optimize computational effort in prostate cancer detection.

Virtual biopsy in prostate cancer: can machine learning distinguish low and high aggressive tumors on MRI?

In the last decades, MRI was proven a useful tool for the diagnosis and characterization of Prostate Cancer (PCa). In the literature, many studies focused on characterizing PCa aggressiveness, but a few have distinguished between low-aggressive (Gleason Grade Group (GG) <=2) and high-aggressive (GG>=3) PCas based on biparametric MRI (bpMRI). In this study, 108 PCas were collected from two different centers and were divided into training, testing, and validation set. From Apparent Diffusion Coefficient (ADC) map and T2-Weighted Image (T2WI), we extracted texture features, both 3D and 2D, and we implemented three different methods of Feature Selection (FS): Minimum Redundance Maximum Relevance (MRMR), Affinity Propagation (AP), and Genetic Algorithm (GA). From the resulting subsets of predictors, we trained Support Vector Machine (SVM), Decision Tree, and Ensemble Learning classifiers on the training set, and we evaluated their prediction ability on the testing set. Then, for each FS method, we chose the best classifier, based on both training and testing performances, and we further assessed their generalization capability on the validation set. Between the three best models, a Decision Tree was trained using only two features extracted from the ADC map and selected by MRMR, achieving, on the validation set, an Area Under the ROC (AUC) equal to 81%, with sensitivity and specificity of 77% and 93%, respectively.Clinical Relevance- Our best model demonstrated to be able to distinguish low-aggressive from high-aggressive PCas with high accuracy. Potentially, this approach could help clinician to noninvasively distinguish between PCas that might need active treatment and those that could potentially benefit from active surveillance, avoiding biopsy-related complications.